Gene Summary

Gene:PVT1; Pvt1 oncogene
Aliases: LINC00079, MIR1204HG, NCRNA00079, onco-lncRNA-100
Summary:This gene represents a long non-coding RNA locus that has been identified as a candidate oncogene. Increased copy number and overexpression of this gene are associated with many types of cancers including breast and ovarian cancers, acute myeloid leukemia and Hodgkin lymphoma. Allelic variants of this gene are also associated with end-stage renal disease attributed to type 1 diabetes. Consistent with its association with various types of cancer, transcription of this gene is regulated by the tumor suppressor p53 through a canonical p53-binding site, and it has been implicated in regulating levels of the proto-oncogene MYC to promote tumorigenesis. [provided by RefSeq, Sep 2015]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Source:NCBIAccessed: 31 August, 2019

Cancer Overview

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Publications Per Year (1994-2019)
Graph generated 31 August 2019 using data from PubMed using criteria.

Literature Analysis

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Tag cloud generated 31 August, 2019 using data from PubMed, MeSH and CancerIndex

Latest Publications: PVT1 (cancer-related)

Li Z, Tan H, Zhao W, et al.
Integrative analysis of DNA methylation and gene expression profiles identifies MIR4435-2HG as an oncogenic lncRNA for glioma progression.
Gene. 2019; 715:144012 [PubMed] Related Publications
Long noncoding RNAs (lncRNAs) have been shown to play an important role in tumor biogenesis and prognosis. The glioma is a grade classified cancer, however, we still lack the knowledge on their function during glioma progression. While previous studies have shown how lncRNAs regulate protein-coding gene epigenetically, it is still unclear how lncRNAs are regulated epigenetically. In this study, we firstly analyzed the RNA-seq data systematically across grades II, IV, and IV of glioma samples. We identified 60 lncRNAs that are significantly differentially expressed over disease progression (DElncRNA), including well-known PVT1, HOTAIR, H19 and rarely studied CARD8-AS, MIR4435-2HG. Secondly, by integrating HM450K methylation microarray data, we demonstrated that some of the lncRNAs are epigenetically regulated by methylation. Thirdly, we developed a DESeq2-GSEA-ceRNA-survival analysis strategy to investigate their functions. Particularly, MIR4435-2HG is highly expressed in high-grade glioma and may have an impact on EMT and TNFα signaling pathway by functioning as a miRNA sponge of miR-125a-5p and miR-125b-5p to increase the expression of CD44. Our results revealed the dynamic expression of lncRNAs in glioma progression and their epigenetic regulation mechanism.

Zou B, Wang D, Xu K, et al.
Prognostic value of long non-coding RNA plasmacytoma variant translocation1 in human solid tumors: A meta-analysis.
Medicine (Baltimore). 2019; 98(27):e16087 [PubMed] Free Access to Full Article Related Publications
Plasmacytoma variant translocation 1 (PVT1) is highly expressed in a variety of cancer tissues and is related to the clinicopathological features and prognosis. However, the prognostic value of PVT1 is still controversial. Therefore, this systematic evaluation and meta-analysis were performed to evaluate the relationship between PVT1 expression and clinicopathological features.PubMed, EMBASE, Web of science, and Cochrane library databases were searched for literature collection according to inclusion criteria and exclusion criteria. The pooled hazard ratios (HRs) or odds ratios (ORs) were used to evaluate the association between PVT1 expression and overall survival, tumor size, tumor-node-metastasis (TNM) stage, lymph node metastasis, and distant metastasis.A total of 39 articles including 3974 patients were included in the study. The results showed that the expression of PVT1 was closely related to the overall survival rate of cancers (HR = 1.64, 95% confidence interval [CI]: 1.50-1.78, P < .000001). Subgroup analysis showed that the high expression of PVT1 was closely related to the low overall survival rate of patients with clear cell renal cell carcinoma, breast cancer, cervical cancer, colon cancer, epithelial ovarian cancer, gastric cancer, lung cancer, and osteosarcoma. In addition, the high expression of PVT1 was positively correlated with tumor size (OR = 1.50, 95% CI: 1.14-1.96, P = .004), TNM stage (OR = 3.39, 95% CI: 2.73-4.20, P < .00001), lymph node metastasis (OR = 2.60, 95% CI: 1.76-3.84, P < .00001), and distant metastasis (OR = 2.94, 95% CI: 1.90-4.56, P < .00001).PVT1 could serve as a marker for the size, TNM stage, metastasis, and prognosis of different type of cancers.

Adhikary J, Chakraborty S, Dalal S, et al.
Circular PVT1: an oncogenic non-coding RNA with emerging clinical importance.
J Clin Pathol. 2019; 72(8):513-519 [PubMed] Related Publications
The importance of circular RNAs (circRNAs) in pathological processes like cancer is evident. Among the circRNAs, recent studies have brought circPVT1 under focus as the most potent oncogenic non-coding RNA. Recent studies on various aspects of circPVT1, including its biogenesis, molecular alteration and its probable role in oncogenesis, have been conducted for research and clinical interest. In this review, a first attempt has been made to summarise the available data on circPVT1 from PubMed and other relevant databases with special emphasis on its role in development, progression and prognosis of various malignant conditions. CircPVT1 is derived from the same genetic locus encoding for long non-coding RNA lncPVT1; however, existing literature suggested circPVT1 and lncPVT1 are transcripted independently by different promoters. The interaction between circRNA and microRNA has been highlighted in majority of the few malignancies in which circPVT1 was studied. Besides its importance in diagnostic and prognostic procedures, circPVT1 seemed to have huge therapeutic potential as evident from differential drug response of cancer cell line as well as primary tumors depending on expression level of the candidate. circPVT1 in cancer therapeutics might be promising as a biomarker to make the existing treatment protocol more effective and also as potential target for designing novel therapeutic intervention.

El-Khazragy N, Elayat W, Matbouly S, et al.
The prognostic significance of the long non-coding RNAs "CCAT1, PVT1" in t(8;21) associated Acute Myeloid Leukemia.
Gene. 2019; 707:172-177 [PubMed] Related Publications
Long non-coding RNA (LncRNA) is recently linked to various types of cancers, CCAT and PVT1 are two LncRNAs linked to t(8;21) associated Acute Myeloid Leukemia, the interplay between CCAT, PVT1 and the MYC proto-oncogene implicated in t(8;21) could present an opportunity for using LncRNA as prognostic biomarker or a target for therapy, We investigated the expression levels of LncRNAs in 70 patients; 30 with t(8;21) positive AML and 40 with t(8;21) negative AML, We found that CCAT1 and PVT1 are expressed in higher levels in t(8;21) positive -AML by 5.3 folds compared to t(8;21) negative group; the expression values were significantly associated with high-risk clinical criteria; moreover, they are associated with lower overall survival (OS) rate and leukemia-free survival (LFS), however we didn't find a statistically significant cut-off value of LncRNAs using the Cox regression analysis for Lnc_PVT1 except with LFS, we conclude that high expression levels of CCAT1 and PVT1 are associated with poor prognosis while being poor prognostic biomarkers in t(8;21) associated AML.

Fang J, Huang J
Clinical significance of the expression of long non-coding RNA PVT1 in glioma.
Cancer Biomark. 2019; 24(4):509-513 [PubMed] Related Publications
BACKGROUND: Glioma is the most common primary malignant tumor in the nervous system.
OBJECTIVE: To investigate the expression of long non-coding RNA Pvt1 oncogene (PVT1) in glioma and its clinical significance.
METHODS: The expression levels of PVT1 were determined in 59 glioma and 10 normal tissue samples using qRT-PCR. The patients were divided into high and low expression groups and analyzed for their relationship with clinicopathological factors and the survival time using the Kaplan-Meier method.
RESULTS: The expression levels of PVT1 were significantly higher in glioma tissues than in normal tissues (p< 0.01) and higher in high grade (III-IV) than in low grade (I-II) tumors (p< 0.01). Analysis showed that the PVT1 level was closely related to glioma grade (p< 0.01), but not to age, gender, Karnofsky performance status (KPS) and tumor size (p> 0.05). Receiver operator characteristic curve analysis showed an area under the curve of 0.835. Log-rank test showed that the prognosis of high PVT1 group was poorer than that of low PVT1 group (p< 0.01).
CONCLUSIONS: PVT1 is highly expressed in gliomas and its level is positively related to WHO glioma grade and prognosis of gliomas. Therefore, it may be explored as a new molecular marker for predicting malignancy and prognosis of gliomas.

Mishra S, Verma SS, Rai V, et al.
Long non-coding RNAs are emerging targets of phytochemicals for cancer and other chronic diseases.
Cell Mol Life Sci. 2019; 76(10):1947-1966 [PubMed] Related Publications
The long non-coding RNAs (lncRNAs) are the crucial regulators of human chronic diseases. Therefore, approaches such as antisense oligonucleotides, RNAi technology, and small molecule inhibitors have been used for the therapeutic targeting of lncRNAs. During the last decade, phytochemicals and nutraceuticals have been explored for their potential against lncRNAs. The common lncRNAs known to be modulated by phytochemicals include ROR, PVT1, HOTAIR, MALAT1, H19, MEG3, PCAT29, PANDAR, NEAT1, and GAS5. The phytochemicals such as curcumin, resveratrol, sulforaphane, berberine, EGCG, and gambogic acid have been examined against lncRNAs. In some cases, formulation of phytochemicals has also been used. The disease models where phytochemicals have been demonstrated to modulate lncRNAs expression include cancer, rheumatoid arthritis, osteoarthritis, and nonalcoholic fatty liver disease. The regulation of lncRNAs by phytochemicals can affect multi-steps of tumor development. When administered in combination with the conventional drugs, phytochemicals can also produce synergistic effects on lncRNAs leading to the sensitization of cancer cells. Phytochemicals target lncRNAs either directly or indirectly by affecting a wide variety of upstream molecules. However, the potential of phytochemicals against lncRNAs has been demonstrated mostly by preclinical studies in cancer models. How the modulation of lncRNAs by phytochemicals produce therapeutic effects on cancer and other chronic diseases is discussed in this review.

Esfandi F, Taheri M, Omrani MD, et al.
Expression of long non-coding RNAs (lncRNAs) has been dysregulated in non-small cell lung cancer tissues.
BMC Cancer. 2019; 19(1):222 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Non-small cell lung cancer (NSCLC) as the most frequent type of lung cancer is associated with extensive mortality. Researchers have studied the suitability of several molecules as biomarkers for early detection of this cancer. Long non-coding RNAs (lncRNAs) as the main regulators of gene expression have also been assessed in this regard.
METHODS: In the present study, we compared expression level of Fas-antisense 1 (FAS-AS1), Growth Arrest Specific 5 (GAS5), PVT1, Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1), taurine upregulated gene 1 (TUG1) and TNFα and hnRNPL related immunoregulatory LincRNA (THRIL) in 32 NSCLC samples and their corresponding adjacent non-cancerous tissues (ANCTs).
RESULTS: NEAT1 has been significantly over-expressed in NSCLC tissues obtained from male subjects compared with the corresponding ANCTs (Relative expression (REx) = 3.022, P = 0.019) but not in female subjects (P = 0.975). FAS-AS1 was significantly down-regulated in NSCLC tissues obtained from both males and females subjects compared with the corresponding ANCTs (REx = - 4.12 and - 3.14, P = 0.015 and 0.033 respectively). TUG1, GAS5, THRIL and HOTAIRM1 were significantly down-regulated in tumoral tissues obtained from male subjects compared with the corresponding ANCTs.
CONCLUSIONS: The observed dysregulation of these lncRNAs in NSCLC tissues compared with the corresponding ANCTs warrants future studies to confirm the results of the current study in larger sample sizes to elaborate their role as cancer biomarkers.

Chen J, Yu Y, Li H, et al.
Long non-coding RNA PVT1 promotes tumor progression by regulating the miR-143/HK2 axis in gallbladder cancer.
Mol Cancer. 2019; 18(1):33 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The long non-coding RNA PVT1 (lncRNA PVT1) has been reported to act as an oncogenic regulator of several cancers. However, its expression and function in gallbladder cancer (GBC) remain largely unknown.
METHODS: In situ hybridization (ISH) and quantitative real-time PCR (qPCR) were performed to detect the expression of PVT1 and miR-143 in GBC tissues and cell lines. Immunohistochemistry (IHC) assays were performed to assess the expression of the hexokinase 2 (HK2) protein. The relationships among PVT1, miR-143 and HK2 were evaluated using dual-luciferase reporter, RNA immunoprecipitation (RIP) and biotin pull-down assays. The biological functions of PVT1, miR-143 and HK2 in GBC cells were explored with cell counting kit 8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU), colony formation, transwell, wound healing and glucose metabolism assays in vitro. For in vivo experiments, a xenograft model was used to investigate the effects of PVT1 and HK2 on GBC.
RESULTS: PVT1 was upregulated in GBC tissues and cells and was positively associated with malignancies and worse overall survival. PVT1 knockdown inhibited cell proliferation, migration, and invasion in vitro and restrained tumor growth in vivo. Further studies demonstrated that PVT1 positively regulated HK2 expression via its competing endogenous RNA (ceRNA) activity on miR-143. Additionally, HK2 expression and function were positively correlated with PVT1. Furthermore, we observed that the PVT1/miR-143/HK2 axis promoted cell proliferation and metastasis by regulating aerobic glucose metabolism in GBC cells.
CONCLUSIONS: The results of our study reveal a potential ceRNA regulatory pathway in which PVT1 modulates HK2 expression by competitively binding to endogenous miR-143 in GBC cells, which may provide new insights into novel molecular therapeutic targets for GBC.

Wu XZ, Cui HP, Lv HJ, Feng L
Knockdown of lncRNA PVT1 inhibits retinoblastoma progression by sponging miR-488-3p.
Biomed Pharmacother. 2019; 112:108627 [PubMed] Related Publications
Emerging evidence suggests that long non-coding RNAs (lncRNAs) play a regulatory role in the pathogenesis and progression of retinoblastoma (RB). lncRNA plasmacytoma variant translocation 1 (PVT1) is highly expressed in a plenty of tumors, and is believed to serve as an oncogene. However, the expression, roles, and action mechanisms of PVT1 in the carcinogenesis and progression of RB are still largely unknown. In this study, we found that PVT1 was upregulated in RB tissues and cell lines. PVT1 levels correlated with optic nerve invasion, and intraocular international retinoblastoma classify (IIRC) stage. In addition, the results demonstrated that patients with RB who showed higher expression of PVT1 had worse overall survivals. In WERI-Rb1 and Y79 cells, PVT1 silencing significantly inhibited cell proliferation, migration, invasion, and cell cycle progression and induced cell apoptosis in vitro. Moreover, in vivo xenograft assay indicated that PVT1 knockdown suppressed the tumor volume and tumor weight. The analysis of the mechanisms of action revealed that the reduction of PVT1 inhibited the expression of notch2 by upregulating miR-488-3p. In general, our results demonstrated that PVT1 may be a novel biomarker for prognosis and a new target for the treatment of RB.

Yang L, Peng X, Jin H, Liu J
Long non-coding RNA PVT1 promotes autophagy as ceRNA to target ATG3 by sponging microRNA-365 in hepatocellular carcinoma.
Gene. 2019; 697:94-102 [PubMed] Related Publications
The pathogenesis and the underlying mechanisms of hepatocellular carcinoma (HCC) remain unclear. LncRNA plasmacytoma variant translocation 1 (PVT1) is an oncogene in a variety of cancers. The role of PVT1 in HCC progression is not completely understood. In the present study, we conducted a series of studies to explore the role of PVT1 on autophagy in HCC cells. Our study found PVT1 levels were markedly up-regulated in the corresponding HCC tissues. Importantly, we found that PVT1 could facilitate cell autophagy in HCC cells. Then, we confirmed that the effect of PVT1 promoting autophagy was dependent on regulating ATG3 expression. Further investigations revealed that PVT1 could upregulate autophagy-related gene 3 (ATG3) expression by acting as an endogenous sponge of miR-365, which was an inhibitor gene on ATG3 protein by targeting 3'UTR of ATG3 mRNA. Moreover, rescue assays indicated that the effect of PVT1 on autophagy of HCC cells were dependent on miR-365. In conclusion, our study demonstrated PVT1 might be a key regulator participating in autophagy in HCC cells. We proved that PVT1 could promote autophagy as ceRNA by targeting miR-365.

Pyfrom SC, Luo H, Payton JE
PLAIDOH: a novel method for functional prediction of long non-coding RNAs identifies cancer-specific LncRNA activities.
BMC Genomics. 2019; 20(1):137 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Long non-coding RNAs (lncRNAs) exhibit remarkable cell-type specificity and disease association. LncRNA's functional versatility includes epigenetic modification, nuclear domain organization, transcriptional control, regulation of RNA splicing and translation, and modulation of protein activity. However, most lncRNAs remain uncharacterized due to a shortage of predictive tools available to guide functional experiments.
RESULTS: To address this gap for lymphoma-associated lncRNAs identified in our studies, we developed a new computational method, Predicting LncRNA Activity through Integrative Data-driven 'Omics and Heuristics (PLAIDOH), which has several unique features not found in other methods. PLAIDOH integrates transcriptome, subcellular localization, enhancer landscape, genome architecture, chromatin interaction, and RNA-binding (eCLIP) data and generates statistically defined output scores. PLAIDOH's approach identifies and ranks functional connections between individual lncRNA, coding gene, and protein pairs using enhancer, transcript cis-regulatory, and RNA-binding protein interactome scores that predict the relative likelihood of these different lncRNA functions. When applied to 'omics datasets that we collected from lymphoma patients, or to publicly available cancer (TCGA) or ENCODE datasets, PLAIDOH identified and prioritized well-known lncRNA-target gene regulatory pairs (e.g., HOTAIR and HOX genes, PVT1 and MYC), validated hits in multiple lncRNA-targeted CRISPR screens, and lncRNA-protein binding partners (e.g., NEAT1 and NONO). Importantly, PLAIDOH also identified novel putative functional interactions, including one lymphoma-associated lncRNA based on analysis of data from our human lymphoma study. We validated PLAIDOH's predictions for this lncRNA using knock-down and knock-out experiments in lymphoma cell models.
CONCLUSIONS: Our study demonstrates that we have developed a new method for the prediction and ranking of functional connections between individual lncRNA, coding gene, and protein pairs, which were validated by genetic experiments and comparison to published CRISPR screens. PLAIDOH expedites validation and follow-on mechanistic studies of lncRNAs in any biological system. It is available at https://github.com/sarahpyfrom/PLAIDOH .

Gu JX, Zhang X, Miao RC, et al.
Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma.
World J Gastroenterol. 2019; 25(2):220-232 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Recent evidence shows that long non-coding RNAs (lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma (HCC). Increasing studies demonstrate that lncRNAs are potential prognostic factors for HCC. Moreover, several studies reported the combination of lncRNAs for predicting the overall survival (OS) of HCC, but the results varied. Thus, more effort including more accurate statistical approaches is needed for exploring the prognostic value of lncRNAs in HCC.
AIM: To develop a robust lncRNA signature associated with HCC recurrence to improve prognosis prediction of HCC.
METHODS: Univariate COX regression analysis was performed to screen the lncRNAs significantly associated with recurrence-free survival (RFS) of HCC in GSE76427 for the least absolute shrinkage and selection operator (LASSO) modelling. The established lncRNA signature was validated and developed in The Cancer Genome Atlas (TCGA) series using Kaplan-Meier curves. The expression values of the identified lncRNAs were compared between the tumor and non-tumor tissues. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. A prognostic nomogram combining the lncRNA signature and clinical characteristics was constructed.
RESULTS: The lncRNA signature consisted of six lncRNAs:
CONCLUSION: We have constructed a six-lncRNA signature for prognosis prediction of HCC. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.

Sun ZY, Jian YK, Zhu HY, Li B
lncRNAPVT1 targets miR-152 to enhance chemoresistance of osteosarcoma to gemcitabine through activating c-MET/PI3K/AKT pathway.
Pathol Res Pract. 2019; 215(3):555-563 [PubMed] Related Publications
BACKGROUND: LncRNA PVT1 has been reported to be involved in a variety of biological processes, including cell proliferation, cell differentiation and cancer progression. However, the mechanism by which LncRNA PVT1 contributes to chemoresistance of osteosarcoma cell, has not been fully elucidated.
METHODS: We first generatedLncRNA PVT1-overexpressed MG63 cells and LncRNA PVT1 knockdown MG63/DOX cells. Then, we examined the effect of LncRNA PVT1 on cell viability and colony formation ability by MTT assay and soft agar assay, respectively. In addition, we performed flow cytometry analysis to detect apoptosis induced by GEM. Dual luciferase reporter assay and RIP were used to confirmed the interaction between LncRNA PVT1 and miR-152. Finally, we determined protein level of c-MET, p-PI3K, and p-AKT by westernblot.
RESULTS: LncRNA PVT1 overexpression promoted cell proliferation and exhibited the anti-apoptotic property in LncRNA PVT1-overexpressing MG63 cells treated with gemcitabine. While, LncRNA PVT1-depleted MG63/DOX cells treated with gemcitabine exhibited significant lower survival rate and high percentage of apoptosis. Next, we found that LncRNA PVT1 could target and downregulated the level of miR-152. Interestingly, miR-152 greatly rescued the biological outcomes of LncRNA PVT1 not only in MG63 but also in MG63/DOX cells. We observed that LncRNA PVT1 markedly induced PI3K/AKT pathway activation, which was abolished by miR-152 mimics overexpression. Finally, c-MET inhibitor was used to confirm the essential role of c-MET in LncRNA PVT1 and miR-152-regulated PI3K/AKT signaling.
CONCLUSION: We showed thatlncRNA PVT1 played a contributory role in chemoresistance of osteosarcoma cells through c-MET/PI3K/AKT pathway activation, which was largely dependent on miR-152. Our findings advance our understanding of how lncRNA PVT1 promotes chemoresistance of osteosarcoma cells and facilitate development of novel strategies for treating osteosarcoma.

Jiang W, He Y, Shi Y, et al.
MicroRNA-1204 promotes cell proliferation by regulating PITX1 in non-small-cell lung cancer.
Cell Biol Int. 2019; 43(3):253-264 [PubMed] Related Publications
MicroRNA-1204 (miR-1204), a member of the PVT1 region, may improve B cell differentiation and metastasis in breast cancer. However, the role of miR-1204 in non-small-cell lung cancer (NSCLC) and its mechanism remain unclear. The GEO public database was first employed to find differentially expressed genes. The expression level of miR-1204 in patient tissues and NSCLC cell lines was determined using qRT-PCR. Cell proliferation assays were performed to investigate the impact of miR-1204 on cell growth. Bioinformatics analysis and dual-luciferase reporter assays were conducted to find potential target genes. Finally, we performed in vivo experiments to identify the effect of miR-1204 on tumor formation in nude mice. It was first found that miR-1204 was overexpressed in NSCLC tissues and cells. miR-1204 increased the proliferation of NSCLC cells and reduced cell cycle arrest in vitro. PITX1 (paired like homeodomain 1) was found as a potential target gene. In addition, PITX1 was also found to be low in expression in NSCLC tissues and cells. To show that PITX1 reversed the function of miR-1204 in promoting proliferation, confirmatory experiments were performed. Moreover, high miR-1204 and low PITX1 expression was highly correlated with tumor size, lymph node metastasis, and the TNM stage in patients diagnosed with NSCLC. Our results suggested that upregulated miR-1204 in NSCLC is associated with NSCLC progression and promotes NSCLC cell proliferation by downregulating PITX1. miR-1204 may act as a poor prognostic factor and a potential therapeutic target for NSCLC.

Li X, Zhang Z, Jiang H, et al.
Circular RNA circPVT1 Promotes Proliferation and Invasion Through Sponging miR-125b and Activating E2F2 Signaling in Non-Small Cell Lung Cancer.
Cell Physiol Biochem. 2018; 51(5):2324-2340 [PubMed] Related Publications
BACKGROUND/AIMS: Circular RNAs (circRNAs) are key regulators in the development and progression of human cancers, however its role in non-small cell lung cancer (NSCLC) tumorigenesis is not well understood. The aim of this study is to identify the expression level of circPVT1 in NSCLC and further investigated its functional relevance with NSCLC progression both in vitro and in vivo.
METHODS: Quantative real-time PCR was used for the measurement of circPVT1 in NSCLC specimens and cell lines. Fluorescence in situ hybridization analysis (FISH) assay was used for the identification of sublocation of circPVT1 in NSCLC cells. Bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to verify the binding of c-Fos at circPVT1 promoter region, and the direct interaction between circPVT1 and miR-125b. Gain- or loss-function assays were performed to evaluate the effects of circPVT1 on cell proliferation and invasion. Western blot and immunohistochemistry assays were performed to detect the protein levels involved in E2F2 pathway.
RESULTS: We found that circPVT1 was upregulated in NSCLC specimens and cells. The transcription factor c-Fos binded to the promoter region of circPVT1, resulting in the overexpression of circPVT1 in NSCLC. Knockdown of circPVT1 suppressed NSCLC cell proliferation, migration and invasion, and increased apoptosis. In addition, circPVT1 mediated NSCLC progression via the regulation of E2F2 signaling pathway. More importantly, circPVT1 was predominantly abundant in the cytoplasm of NSCLC cells, and circPVT1 could serve as a competing endogenous RNA to regulate E2F2 expression and tumorigenesis in a miR-125b-dependent manner, which is further verified by using an in vivo xenograft model.
CONCLUSION: circPVT1 promotes NSCLC cell growth and invasion, and may serve as a promising therapeutic target for NSCLC patients. Therefore, silence of circPVT1 could be a future direction to develop a novel treatment strategy.

Moschovis D, Vasilaki E, Tzouvala M, et al.
Association between genetic polymorphisms in long non-coding RNAs and pancreatic cancer risk.
Cancer Biomark. 2019; 24(1):117-123 [PubMed] Related Publications
BACKGROUND: Long non-coding RNAs (lncRNAs) are emerging as candidate biomarkers of cancer, having regulatory functions in both oncogenic and tumor-suppressive pathways. Concerning pancreatic cancer (PC), deregulation of lncRNAs involved in tumor initiation, invasion, and metastasis seem to play a key role. However, data is scarce about regulatory mechanism of lncRNA expression.
OBJECTIVE: The aim of our study was to investigate the contribution of two lncRNAs polymorphisms (rs1561927 and rs4759313 of PVT1 and HOTAIR, respectively) in PC susceptibility.
METHODS: A case-control study was conducted analysing rs1561927 and rs4759313 polymorphisms using DNA collected in a population-based case-control study of pancreatic cancer (111 pancreatic ductal adenocarcinoma cases (PDAC), 56 pancreatic neuroendocrine tumor (PNET), and 125 healthy controls).
RESULTS: Regarding the PVT1 rs1561927 polymorphism the G allele was significantly overrepresented in both PDAC and PNET patients compared to the controls, while the presence of the HOTAIR rs4759314 G allele was found to be overrepresented in the PNET patients only compared to the controls. The PVT1 rs1561927 AG/GG genotypes were associated with poor overall survival in PDAC patients.
CONCLUSIONS: Our results suggested that polymorphisms of these two lncRNA polymorphisms implicated in pancreatic carcinogenesis. Further large-scale and functional studies are needed to confirm our results.

Wang L, Wang R, Ye Z, et al.
PVT1 affects EMT and cell proliferation and migration via regulating p21 in triple-negative breast cancer cells cultured with mature adipogenic medium.
Acta Biochim Biophys Sin (Shanghai). 2018; 50(12):1211-1218 [PubMed] Related Publications
Excessive adiposity has long been proved to be associated with greater incidence and mortality of breast cancer in post-menopausal women. However, the effects and underlying mechanisms of human adipocytes on breast cancer cells remain largely unknown. In recent years, several reports have revealed the oncogenic role of long non-coding RNA PVT1 in breast cancer. Here, we aimed to investigate the role and underlying mechanisms of PVT1 in triple-negative breast cancer (TNBC) cells cultured with mature adipogenic medium. At first, we successfully induced adipogenic differentiation from human adipose-derived mesenchymal stem cells and collected the mature adipogenic medium to mimic excessive adiposity. Our results demonstrated that the mature adipogenic medium promoted the epithelial-mesenchymal transition, enhanced the cell viability and migration potential of TNBC cells. In addition, we proved that mature adipogenic medium affected the PVT1 expression and inhibition of the PVT1 disturbed the role of mature adipogenic medium in TNBC cells. Finally, we illustrated that repression of p21 restored the phenotype caused by PVT1 knockdown in TNBC cells treated with mature adipogenic medium. Taken together, our results demonstrated that PVT1 affected the role of mature adipogenic medium in TNBC cells via modulating p21 expression.

Song T, Yan L, Cai K, et al.
Downregulation of long noncoding RNA PVT1 attenuates paclitaxel resistance in glioma cells.
Cancer Biomark. 2018; 23(3):447-453 [PubMed] Related Publications
BACKGROUND: Drug resistance in clinical cancer treatment has become an issue.
OBJECTIVE: We focus on abnormally expressed lncRNAs in glioma and investigating the function of PVT1.
METHODS: The paclitaxel-resistant glioma cells SHG-44 RE was obtained through screening the SHG 44 cells that were cultured in medium containing a certain concentration of paclitaxel. Cell survival of SHG 44 RE and SHG 44 cells under the treatment of paclitaxel was detected by MTT assay. The aberrant expressed lncRNAs were screened out with microarray analysis. Further qRT-PCR was utilized to validate the expression of lncRNA PVT1 in the two cells. After manipulating the expression of PVT1, cell viability and apoptosis were measured by MTT and flow cytometry respectively.
RESULTS: LncRNA PVT1 was overexpressed in glioma cells SHG-44 RE compared with parent SHG-44 cells. Down-regulation of lncRNA PVT1 inhibited the SHG-44 RE cell viability and increased glioma SHG-44 RE cells apoptosis after paclitaxel treatment, suggesting that inhibition of lncRNA PVT1 improved paclitaxel sensibility in human glioma cells.
CONCLUSION: Down-regulation of PVT1 could enhance chemosensitivity of paclitaxel, induce apoptosis of glioma cells and noteworthy inhibit glioma cells proliferation. Our findings of PVT1 could contribute to attenuate paclitaxel resistance in clinical medicine.

You L, Wang H, Yang G, et al.
Gemcitabine exhibits a suppressive effect on pancreatic cancer cell growth by regulating processing of PVT1 to miR1207.
Mol Oncol. 2018; 12(12):2147-2164 [PubMed] Free Access to Full Article Related Publications
Gemcitabine serves as a first-line chemotherapy agent for advanced pancreatic cancer (PC). However, the molecular basis by which gemcitabine exerts its effects is not well-established, and the targeted genetic pathways remain unclear. Pvt1 oncogene (non-protein coding) (PVT1) has been reported to be an oncogenic long non-coding RNA in tumorigenesis. In the present study, we show that the expression of PVT1 is correlated with gemcitabine efficacy in PC therapy. Inhibition of PVT1 led to decreased cell growth in PC cells treated with gemcitabine. We also demonstrate that gemcitabine treatment decreases PVT1 levels and increases its encoded miRNAs, such as the miR-1207 pair (miR-1207-5p/3p). Overexpression of the miR-1207 pair enhanced the chemosensitivity of cells to gemcitabine, whereas silencing of miR-1207-5p/3p to prevent its induction by gemcitabine treatment led to increased cell growth. Mechanistic studies revealed that miR-1207-5p and miR-1207-3p target the SRC proto-oncogene (non-receptor tyrosine kinase) and ras homolog family member A in PC cells, respectively. In particular, we observed that gemcitabine induced Drosha ribonuclease III (Drosha) and DGCR8 microprocessor complex subunit (DGCR8) upregulation and then triggered PVT1 processing. Suppression of Drosha and DGCR8 contributed to a dampened efficacy of gemcitabine, indicating that gemcitabine decreased PVT1 expression by promoting its processing into miRNAs, which in turn resulted in blunted oncogenic signaling in PC cells. Moreover, we demonstrate that gemcitabine chemoresistance was a result of decreased expression of Drosha and DGCR8 in AsPC-1 cells and tumor cell-engrafted models. Overall, our findings define a novel mechanism for understanding the efficacy of gemcitabine chemotherapy in PC.

Han BW, Ye H, Wei PP, et al.
Global identification and characterization of lncRNAs that control inflammation in malignant cholangiocytes.
BMC Genomics. 2018; 19(1):735 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Long noncoding RNAs (lncRNAs) are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis, and associated with chronic inflammation and damage to the biliary epithelium. This study determined whether lncRNAs were dysregulated and participated in disease diagnosis or pivotal inflammation pathways through a genome-wide lncRNA screening and functional analysis.
RESULTS: We firstly identified a large number of lncRNAs abnormally expressed between 9 pairs of cancerous and adjacent tissues of CCA, and between intra-hepatic CCA and extra-hepatic CCA through a genome-wide profiling. A set of aberrant differentially expressed lncRNAs were further validated in a training set (16 pairs) and a test set (11 pairs) of CCA patient samples. Following assessment of the diagnostic value of the 7 differentially expressed lncRNAs, we confirmed the optimal combination of H19, C3P1, AC005550.3, PVT1, and LPAL2 with area under the curve of 0.8828 [95% CI: 0.7441-1.021, P < 0.001], with 93.75% sensitivity and 81.25% specificity, at the cutoff point of - 0.2884 to distinguish the CCA tissue from the normal ones, suggesting that specific lncRNAs may have potential for detecting CCA. More importantly, the genome-wide locus and lncRNA/mRNA co-expression analyses revealed a set of lncRNAs that participated in inflammation and oxidative stress response pathways by regulating genes in cis or in trans. Finally, APOC1P1, PVT1, and LPAL2 were validated to regulate the migration and some pivotal inflammation genes under the CCA pathogenesis.
CONCLUSIONS: Our findings are the first to show that lncRNAs may not only be potential biomarkers of CCA progression but also respond to inflammation in CCA.

Jeannot E, Harlé A, Holmes A, Sastre-Garau X
Nuclear factor I X is a recurrent target for HPV16 insertions in anal carcinomas.
Genes Chromosomes Cancer. 2018; 57(12):638-644 [PubMed] Related Publications
Anal carcinomas (AC) are associated with human papillomavirus (HPV) DNA sequences, but little is known about the physical state of the viral genome in carcinoma cells. To define the integration status and gene(s) targeted by viral insertions in AC, tumor DNAs extracted from 35 tumor specimen samples in patients with HPV16-associated invasive carcinoma were analyzed using the detection of integrated papillomavirus sequences-PCR approach. The genomic status at integration sites was assessed using comparative genomic hybridization-array assay and gene expression using reverse transcription quantitative PCR (RT-qPCR). HPV16 DNA was found integrated in 25/35 (71%) cases and the integration locus could be determined at the molecular level in 19 cases (29 total integration loci). HPV DNA was inserted on different chromosomes, but 5 cases harbored viral sequences at 19p13.2, within the nuclear factor I X (NFIX) locus. Viral DNA mapped between the most distal and the two proximal alternatively expressed exons of this gene in three cases (CA21, CA04, and CA35) and upstream of this gene (663 kb and 2.3 Mb) in the others. CGH arrays showed genomic gains/amplifications at the NFIX region, associated with HPV within the gene and RT-qPCR, revealed NFIX mRNA overexpression. Other genes targeted by integration were IL20RB, RPS6KA2, MSRA1, PIP5K1B, SLX4IP, CECR1, BCAR3, ATF6, CSNK1G1, APBA2, AGK, ILF3, PVT1, TRMT1, RAD51B, FASN, CCDC57, DSG3, and ZNF563. We identified recurrent targeting of NFIX by HPV16 insertion in anal carcinomas, supporting a role for this gene in oncogenesis, as reported for non-HPV tumors.

Dennison KL, Chack AC, Hickman MP, et al.
Ept7, a quantitative trait locus that controls estrogen-induced pituitary lactotroph hyperplasia in rat, is orthologous to a locus in humans that has been associated with numerous cancer types and common diseases.
PLoS One. 2018; 13(9):e0204727 [PubMed] Free Access to Full Article Related Publications
Pituitary adenoma is a common intracranial neoplasm that is observed in approximately 10% of unselected individuals at autopsy. Prolactin-producing adenomas, i.e., prolactinomas, comprise approximately 50% of all pituitary adenomas and represent the most common class of pituitary tumor. Multiple observations suggest that estrogens may contribute to development of prolactinoma; however, direct evidence for a causal role of estrogens in prolactinoma etiology is lacking. Rat models of estrogen-induced prolactinoma have been utilized extensively to identify the factors, pathways and processes that are involved in pituitary tumor development. The objective of this study was to localize to high resolution Ept7 (Estrogen-induced pituitary tumor), a quantitative trait locus (QTL) that controls lactotroph responsiveness to estrogens and was mapped to rat chromosome 7 (RNO7) in an intercross between BN and ACI rats. Data presented and discussed herein localize the Ept7 causal variant(s) to a 1.91 Mb interval of RNO7 that contains two protein coding genes, A1bg and Myc, and Pvt1, which yields multiple non-protein coding transcripts of unknown function. The Ept7 orthologous region in humans is located at 8q24.21 and has been linked in genome wide association studies to risk of 8 distinct epithelial cancers, including breast, ovarian, and endometrial cancers; 3 distinct types of B cell lymphoma; multiple inflammatory and autoimmune diseases; and orofacial cleft defects. In addition, the Ept7 locus in humans has been associated with variation in normal hematologic and development phenotypes, including height. Functional characterization of Ept7 should ultimately enhance our understanding of the genetic etiology of prolactinoma and these other diseases.

Tonon L, Fromont G, Boyault S, et al.
Mutational Profile of Aggressive, Localised Prostate Cancer from African Caribbean Men Versus European Ancestry Men.
Eur Urol. 2019; 75(1):11-15 [PubMed] Related Publications
Causes of high mortality of prostate cancer in men of African ancestry living in the French West Indies are still debated, between suspicions of environmental factors and genetic susceptibility. We report an integrated genomic study of 25 tumour tissues from radical prostatectomy of aggressive (defined by International Society of Urological Pathology ≥3) prostate cancer patients (10 African Caribbean and 15 French Caucasian) using single nucleotide polymorphism arrays, whole-genome sequencing, and RNA sequencing. The results show that African Caribbean tumours are characterised by a more frequent deletion at 1q41-43 encompassing the DNA repair gene PARP1, and a higher proportion of intrachromosomal rearrangements including duplications associated with CDK12 truncating mutations. Transcriptome analyses show an overexpression of genes related to androgen receptor activity in African Caribbean tumours, and of PVT1, a long non-coding RNA located at 8q24 that confirms the strong involvement of this region in prostate tumours from men of African ancestry. Patient summary: Mortality of prostate cancer is higher in African Caribbean men than in French Caucasian men. Specificities of the former could be explained by genomic events linked with key genes such as DNA damage pathway genes PARP1, CDK12, and the oncogenic long non-coding RNA gene PVT1 at the 8q24 prostate cancer susceptibility locus.

Xu Y, Luo X, He W, et al.
Long Non-Coding RNA PVT1/miR-150/ HIG2 Axis Regulates the Proliferation, Invasion and the Balance of Iron Metabolism of Hepatocellular Carcinoma.
Cell Physiol Biochem. 2018; 49(4):1403-1419 [PubMed] Related Publications
BACKGROUND/AIMS: To investigate the biological roles and underlying molecular mechanisms of long non-coding RNA (lncRNA) PVT1 in Hepatocellular carcinoma (HCC).
METHODS: qRT-PCR was performed to measure the expression of miRNA and mRNA. Western blot was performed to measure the protein expression. CCK-8 assay was performed to determine cell proliferation. Flow cytometry was performed to detect cell apoptosis. Wounding-healing assay and Transwell assay was performed to detect cell migration and invasion. Dual luciferase reporter assay was performed to verify the target relationship. Quantichrom iron assay was performed to check uptake level of cellular iron.
RESULTS: PVT1 expression was up-regulated in HCC tissues and cell lines. Function studies revealed that PVT1 knockdown significantly suppressed cell proliferation, migration and invasion, and induced cell apoptosis in vitro. Furthermore, PVT1 could directly bind to microRNA (miR)-150 and down-regulate miR-150 expression. Hypoxia-inducible protein 2 (HIG2) was found to be one target gene of miR-150, and PVT1 knockdown could inhibit the expression of HIG2 through up-regulating miR-150 expression. In addition, the expression of miR-150 was down-regulated, while the expression of HIG2 was up-regulated in HCC tissues and cell lines. Moreover, inhibition of miR-150 could partly reverse the biological effects of PVT1 knockdown on proliferation, motility, apoptosis and iron metabolism in vitro, which might be associated with dysregulation of HIG2. In vivo results showed that PVT1 knockdown suppressed tumorigenesis and iron metabolism disorder by regulating the expression of miR-150 and HIG2.
CONCLUSION: Taken together, the present study demonstrates that PVT1/miR-150/HIG2 axis may lead to a better understanding of HCC pathogenesis and provide potential therapeutic targets for HCC.

Zhao K, Zhao Y, Zhu JY, et al.
A Panel of Genes Identified as Targets for 8q24.13-24.3 Gain Contributing to Unfavorable Overall Survival in Patients with Hepatocellular Carcinoma.
Curr Med Sci. 2018; 38(4):590-596 [PubMed] Related Publications
Copy number aberrations (CNAs) in chromosome arm 8q have been associated with unfavorable clinical outcomes of several cancers and progressive tumor characteristics of hepatocellular carcinoma (HCC). This study was to identify correlation of CNAs in 8q with clinical outcomes of HCC patients, and further screen for differentially expressed genes in outcome-related CNAs. Array comparative genomic hybridization and expression arrays were performed to detect CNAs and expression levels, respectively. The correlations between CNAs in 8q and outcomes were analyzed in 66 patients, with a median follow-up time of 45.0 months (range, 2.6-108.6 months). One hundred and nine cases were further evaluated to identify differentially expressed genes in the potential outcome-related CNAs. Copy number gain in 8q was observed in 22 (33.3%) of the 66 HCC cases. The most recurrent gains (with frequencies >20%) were 8q13.3-21.3,8q21.3-23.3,8q23.3-24.13,8q24.13-24.3, and 8q24.3. Survival analysis showed that 8q24.13-24.3 gain was significantly associated with reduced overall survival (jP=0.010). Multivariate Cox analysis identified 8q24.13-24.3 gain as an independent prognostic factor for poor overall survival (HR=2.47; 95% CI=1.16-5.26; Р=0.019). Apanel of 17 genes within the 8q24.13-24.3 region, including ATAD2,SQLE,PVT1,ASAP1, and NDRG1 were significantly upregulated in HCCs with 8q24.13-24.3 gain compared to those without. These results suggest that copy number gain at 8q24.13-24.3 is an unfavorable prognostic marker for HCC patients, and the potential oncogenes ATAD2,SQLE, PVT1, ASAP1,and NDRG1 within the regional gain, may contribute coordinately to the 8q24.13-24.3 gain-related poor prognosis.

Fu C, Li D, Zhang X, et al.
LncRNA PVT1 Facilitates Tumorigenesis and Progression of Glioma via Regulation of MiR-128-3p/GREM1 Axis and BMP Signaling Pathway.
Neurotherapeutics. 2018; 15(4):1139-1157 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
The current research was aimed at probing into the role of long noncoding RNA (lncRNA) PVT1 in the pathogenesis of glioma and the regulatory mechanism of PVT1/miR-128-3p/GREM1 network in glioma via regulation of the bone morphogenetic protein (BMP) signaling pathway. Microarray analysis was used for preliminary screening for candidate lncRNAs and mRNAs in glioma tissues. Real-time quantitative polymerase chain reaction, Western blot, MTT assay, flow cytometry, migration and invasion assays, and xenograft tumor model were utilized to examine the influence of the lncRNA PVT1/miR-128-3p/GREM1 network on the biological functions of glioma cells. Luciferase assay and RNA-binding protein immunoprecipitation assay were used to validate the miR-128-3p-target relationships with lncRNA PVT1 or GREM1. In addition, the impact of GREM1 on BMP signaling pathway downstream proteins BMP2 and BMP4 was detected via Western blot. LncRNA PVT1 was highly expressed in human glioma tissues and significantly associated with WHO grade (I-II vs III-IV; p < 0.05). There existed a regulatory relationship between lncRNA PVT1 and miR-128-3p as well as that between miR-128-3p and GREM1. MiR-128-3p was downregulated, whereas GREM1 was upregulated in glioma tissues in comparison with para-carcinoma tissues. Overexpression of GREM1 promoted the proliferation and metastatic potential of glioma cells, whereas miR-128-3p mimics inhibited the glioma cell activity through targeting GREM1. Furthermore, lncRNA PVT1 acted as a sponge of miR-128-3p and, thus, influenced the BMP signaling pathway downstream proteins BMP2 and BMP4 through regulating GREM1. LncRNA PVT1 modulated GREM1 and BMP downstream signaling proteins through sponging miR-128-3p, thereby promoting tumorigenesis and progression of glioma.

He F, Song Z, Chen H, et al.
Long noncoding RNA PVT1-214 promotes proliferation and invasion of colorectal cancer by stabilizing Lin28 and interacting with miR-128.
Oncogene. 2019; 38(2):164-179 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Long noncoding RNAs (lncRNAs) are implicated in human cancer, but their mechanisms of action are largely unknown. In this study, we investigated lncRNA alterations that contribute to colorectal cancer (CRC) through microarray expression profiling in CRC patient samples. Here, we report that the CRC-associated lncRNA PVT1-214 is a key regulator of CRC development and progression; patients with high PVT1-214 expression had a shorter survival and poorer prognosis. In vitro and in vivo investigation of the role of PVT1-214 revealed a complex integrated phenotype affecting cell growth, stem-like properties, migration, and invasion. Furthermore, using RNA pull-down and mass spectrometry, we found that Lin28 (also known as Lin28A), a highly conserved RNA-binding protein, is associated with PVT1-214. Strikingly, we found that PVT1-214 not only upregulated Lin28 protein expression in CRC cells by stabilizing Lin28, but also participated in crosstalk with Lin28 mRNA through competition for miR-128 binding, imposing an additional level of post-transcriptional regulation. In addition, we further show that PVT1-214 repressed expression of let-7 family miRNAs, which was abrogated by Lin28 knockdown. Taken together, our findings support a model in which the PVT1-214/Lin28/let-7 axis serves as a critical regulator of CRC pathogenesis, which may simulate a new direction for CRC therapeutic development.

Huang F, Chen W, Peng J, et al.
LncRNA PVT1 triggers Cyto-protective autophagy and promotes pancreatic ductal adenocarcinoma development via the miR-20a-5p/ULK1 Axis.
Mol Cancer. 2018; 17(1):98 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
BACKGROUND: Defective autophagy is thought to contribute to the pathogenesis of many diseases, including cancer. Human plasmacytoma variant translocation 1 (PVT1) is an oncogenic long non-coding RNA that has been identified as a prognostic biomarker in pancreatic ductal adenocarcinoma, but how PVT1 operates in the regulation of autophagy in pancreatic ductal adenocarcinoma (PDA) is unclear.
METHODS: PVT1 expression level was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and hybridization in situ (ISH). Western blot or qRT-PCR was performed to assess the ULK1 protein or mRNA level. Autophagy was explored via autophagic flux detection under a confocal microscope and autophagic vacuoles investigation under a transmission electron microscopy (TEM). The biological role of PVT1 in autophagy and PDA development was determined by gain-of-function and loss-of-function assays.
RESULTS: We found that PVT1 levels paralleled those of ULK1 protein in PDA cancer tissues. PVT1 promoted cyto-protective autophagy and cell growth by targeting ULK1 both in vitro and in vivo. Moreover, high PVT1 expression was associated with poor prognosis. Furthermore, we found that PVT1 acted as sponge to regulate miR-20a-5p and thus affected ULK1 expression and the development of pancreatic ductal adenocarcinoma.
CONCLUSIONS: The present study demonstrates that the "PVT1/miR-20a-5p/ULK1/autophagy" pathway modulates the development of pancreatic ductal adenocarcinoma and may be a novel target for developing therapeutic strategies for pancreatic ductal adenocarcinoma.

Zhang Y, Wen DY, Zhang R, et al.
A Preliminary Investigation of PVT1 on the Effect and Mechanisms of Hepatocellular Carcinoma: Evidence from Clinical Data, a Meta-Analysis of 840 Cases, and In Vivo Validation.
Cell Physiol Biochem. 2018; 47(6):2216-2232 [PubMed] Related Publications
BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) remains a difficult problem that significantly affects the survival of the afflicted patients. Accumulating evidence has demonstrated the functions of long non-coding RNA (lncRNA) in HCC. In the present study, we aimed to explore the potential roles of PVT1 in the tumorigenesis and progression of HCC.
METHODS: In this study, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was applied to detect the differences between PVT1 expression in HCC tissues and cell lines. Then, the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were searched to confirm the relationship between PVT1 expression and HCC. Moreover, a meta-analysis comprising TCGA, GEO, and RT-qPCR was applied to estimate the expression of PVT1 in HCC. Then, cell proliferation was evaluated in vitro. A chicken chorioallantoic membrane (CAM) model of HCC was constructed to measure the effect on tumorigenicity in vivo. To further explore the sponge microRNA (miRNA) of PVT1 in HCC, we used TCGA, GEO, a gene microarray, and target prediction algorithms. TCGA and GEO and the gene microarray were used to select the differentially expressed miRNAs, and the different target prediction algorithms were applied to predict the target miRNAs of PVT1.
RESULTS: We found that PVT1 was markedly overexpressed in HCC tissue than in normal liver tissues based on both RT-qPCR and data from TCGA, and the overexpression of PVT1 was closely related to the gender and race of the patient as well as to higher HCC tumor grades. Also, a meta-analysis of 840 cases from multiple sources (TCGA, GEO and the results of our in-house RT-qPCR) showed that PVT1 gained moderate value in discriminating HCC patients from normal controls, confirming the results of RT-qPCR. Additionally, the upregulation of PVT1 could promote HCC cell proliferation in vitro and vivo. Based on the competing endogenous RNA (ceRNA) theory, the PVT1/miR-424-5p/INCENP axis was finally selected for further research. The in silico prediction revealed that there were complementary sequences between PVT1 and miR-424-5p as well as between miR-424-5p and INCENP. Furthermore, a negative correlation trend was found between miR-424-5p and PVT1 based on RT-qPCR, whereas a positive correlation trend was found between PVT1 and INCENP based on data from TCGA. Also, INCENP small interfering RNA (siRNA) could significantly inhibit cell proliferation and viability.
CONCLUSIONS: We hypothesized that PVT1 could affect the biological function of HCC cells via targeting miR-424-5p and regulating INCENP. Focusing on the new insight of the PVT1/miR-424-5p/INCENP axis, this study provides a novel perspective for HCC therapeutic strategies.

Yang Q, Yu Y, Sun Z, Pan Y
Long non-coding RNA PVT1 promotes cell proliferation and invasion through regulating miR-133a in ovarian cancer.
Biomed Pharmacother. 2018; 106:61-67 [PubMed] Related Publications
The long non-coding RNA, plasmacytoma variant translocation 1 (PVT1), was reportedly to be highly expressed in a variety of tumors including ovarian cancer (OC). However, the role and mechanism of action of PVT1 in the carcinogenesis and progression of OC remains largely unknown. PVT1 and miR-133a expression were detected by quantitative real time PCR(qRT-PCR) assays in OC tissues and cell lines. Cell Counting Kit-8 (CCK-8), flow cytometer, wound healing and transwell invasion assays were performed to evaluate cell proliferation, cycle, migration and invasion abilities, respectively. qRT-PCR and luciferase reporter assays demonstrated PVT1 regulated miR-133a expression. Here, we discovered that PVT1 shows higher expression in OC tissues than in normal ovarian tissues, and patients who show higher expression of PVT1 have worse progression-free and overall survivals compared to lower expression of PVT1. Additionally, we observed that knockdown of PVT1 significantly inhibited OC cell proliferation, and decreased the migration and invasion capabilities of OC cells. Mechanistically, miR-133a was identified to serve as a direct downstream target of PVT1 in OC. Knockdown of PVT1 inhibited cell proliferation, migration and invasion through negative regulating miR-133a in OC cells. Taken together, our finding shows that PVT1 may be a novel biomarker for prognosis and a promising therapeutic target for OC.

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