Gene Summary

Gene:MYCBP; MYC binding protein
Aliases: AMY-1
Summary:The protein encoded by this gene binds to the N-terminus of the oncogenic protein C-MYC, enhancing the ability of C-MYC to activate E box-dependent transcription. The encoded protein is normally found in the cytoplasm, but it translocates to the nucleus during S phase of the cell cycle and associates with C-MYC. This protein may be involved in spermatogenesis. This gene can be silenced by microRNA-22. Two transcript variants, one protein-coding and the other probably not protein-coding, have been found for this gene. [provided by RefSeq, Nov 2011]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:C-Myc-binding protein
Source:NCBIAccessed: 01 September, 2019


What does this gene/protein do?
Show (9)

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 01 September 2019 using data from PubMed using criteria.

Literature Analysis

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Tag cloud generated 01 September, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (5)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: MYCBP (cancer-related)

Li C, Tan F, Pei Q, et al.
Non-coding RNA MFI2-AS1 promotes colorectal cancer cell proliferation, migration and invasion through miR-574-5p/MYCBP axis.
Cell Prolif. 2019; 52(4):e12632 [PubMed] Related Publications
OBJECTIVE: Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play essential roles in the tumour progression. LncRNAs mostly act as competing endogenous RNAs (ceRNAs) by sponging miRNAs. This study aimed to study the association of a novel lncRNA MFI2-AS1 with miR-574-5p/MYCBP axis in the development of colorectal cancer (CRC).
METHODS: Ninety-four CRC tissues and paired adjacent non-tumour tissues were included in our study. The relative expression level of MFI2-AS1 was detected, and its relationship with clinico-pathological factors was analysed. Then, the CRC cells lines (LoVo and RKO) were transfected with MFI2-AS1 siRNA, miR-574-5p mimics and inhibitors. Cell proliferation, migration, invasion, cell cycle distribution and DNA damage in response to different transfection conditions were examined. Dual-luciferase reporter assay was performed to identify the target interactions between MFI2-AS1 and miR-574-5p, miR-574-5p and MYCBP.
RESULTS: LncRNA MFI2-AS1 and MYCBP were up-regulated in CRC tissues when compared with adjacent non-tumour tissues. The expression levels of MFI2-AS1 were significantly associated with tumour histological grade, lymph and distant metastasis, TNM stage and vascular invasion. Both MFI2-AS1 siRNA and miR-574-5p mimics inhibited proliferation, migration and invasion in LoVo and RKO cells. The transfection of miR-574-5p inhibitor showed MFI2-AS1 siRNA-induced changes in CRC cells. Dual-luciferase reporter assay revealed target interactions between MFI2-AS1 and miR-574-5p, miR-574-5p and MYCBP.
CONCLUSIONS: These findings suggested that lncRNA MFI2-AS1 and MYCBP have promoting effects in CRC tissues. LncRNA MFI2-AS1 promoted CRC cell proliferation, migration and invasion through activating MYCBP and by sponging miR-574-5p.

Kazi A, Xiang S, Yang H, et al.
GSK3 suppression upregulates β-catenin and c-Myc to abrogate KRas-dependent tumors.
Nat Commun. 2018; 9(1):5154 [PubMed] Free Access to Full Article Related Publications
Mutant KRas is a significant driver of human oncogenesis and confers resistance to therapy, underscoring the need to develop approaches that disable mutant KRas-driven tumors. Because targeting KRas directly has proven difficult, identifying vulnerabilities specific for mutant KRas tumors is an important alternative approach. Here we show that glycogen synthase kinase 3 (GSK3) is required for the in vitro and in vivo growth and survival of human mutant KRas-dependent tumors but is dispensable for mutant KRas-independent tumors. Further, inhibiting phosphorylation of GSK3 substrates c-Myc on T58 and β-catenin on S33/S37/T41 and their subsequent upregulation contribute to the antitumor activity of GSK3 inhibition. Importantly, GSK3 blockade inhibits the in vivo growth of G12D, G12V, and G12C mutant KRas primary and metastatic patient-derived xenografts from pancreatic cancer patients who progressed on chemo- and radiation therapies. This discovery opens new avenues to target mutant KRas-dependent cancers.

Azarnezhad, Tabrizi, Javan, Mehdipour P
Detection of CCND1 , C-MYC , and FGFR1 amplification using modified SYBR Green qPCR and FISH in breast cancer
Turk J Med Sci. 2018; 48(4):759-767 [PubMed] Related Publications
Background/aim: The aims of this study were to detect CCND1 , C-MYC , and FGFR1 amplification using qPCR, confirmation with FISH, and to further assess their clinicopathological relevance.
Materials and methods: Thirty-five breast tumor samples were analyzed for amplification of the selected genes using modified SYBR Green qPCR. The accuracy of the qPCR was assessed by FISH as a gold-standard method.
Results: CCND1 , C-MYC , and FGFR1 amplifications were observed in 34.28%, 28.57%, and 17.14% of the 35 samples, respectively. qPCR results were significantly confirmed by FISH and qPCR and FISH showed excellent correlation (P = 0.000). CCND1 amplification with tumor stage (P = 0.044), positive metastatic status (P = 0.042), positive family history (P = 0.042), and C-MYC status (P = 0.005); C-MYC amplification with tumor size (P = 0.021), tumor grade (P = 0.018), tumor stage (P = 0.032), and FGFR1 status (P < 0.000); and FGFR1 amplification with tumor size (P = 0.041) and positive ER status (P = 0.042) were statistically associated.
Conclusion: Our findings revealed that the applied qPCR approach could precisely quantify the relative gene copy number. More studies with a larger sample size are suggested to confirm the clinicopathological value of CCND1 , C-MYC , and FGFR1 amplification.

Marimuthu M, Andiappan M, Wahab A, et al.
Canonical Wnt pathway gene expression and their clinical correlation in oral squamous cell carcinoma.
Indian J Dent Res. 2018 May-Jun; 29(3):291-297 [PubMed] Related Publications
Aim: The aim of this study is to explore the prognostic significance and clinicopathological correlations of the Wnt pathway genes in a cohort of surgically treated patients with oral squamous cell carcinoma (OSCC) patients.
Settings and Design: A prospective genetic study on patients with OSCC was carried out during the period from July 2014 to January 2016. Informed consent from patients and institutional ethical approval for the study was obtained and the guidelines were strictly followed for collection of samples.
Subjects and Methods: Clinical data and mRNA expression analysis of ten genes in the canonical Wnt pathway were evaluated and their relationships with clinical and demographic variables were studied in 58 tissue samples. Wnt-3a, β-catenin, secreted frizzled-related proteins sFRP-1, sFRP-2, sFRP-4, sFRP-5, Wnt inhibitory factor 1, dickkopf-1, c-MYC, and cyclin-D1 from cancer (n = 29) and normal (n = 29) tissue samples were investigated using quantitative reverse transcription-polymerase chain reaction.
Statistical Analysis: Descriptive statistics were used to summarize the sample characteristics and clinical variables. If the data were normal, then parametric tests were used; otherwise, nonparametric alternatives were used. All the analyses were carried out using SPSS version 23.0 (IBM SPSS Inc., USA).
Results: Expression of sFRP-1, sFRP-2, and sFRP-5 in control samples and expression of c-MYC and cyclin D1 in cancer samples showed statistical significance. Significant expression of Wnt3A was observed among patients who had recurrence and were deceased.
Conclusion: Wnt3A, β-catenin, and cyclin D1 are recognized as key components of Wnt/β-catenin signaling. However, in this study, there was no significant expression of all the three genes in OSCC. The proto-oncogene c-MYC showed statistically significant upregulation in cancer tissue samples suggesting that the OSCC among South Indian population is primarily not mediated by the canonical Wnt signaling pathway.

Wang F, Sun Y
Overexpression of Myosin Phosphatase Target Subunit 1 (MYPT1) Inhibits Tumor Progression and Metastasis of Gastric Cancer.
Med Sci Monit. 2018; 24:2508-2517 [PubMed] Free Access to Full Article Related Publications
BACKGROUND Myosin phosphatase target subunit 1 (MYPT1) serves as a subgroup of myosin phosphatases, and is frequently low-expressed in human cancers. However, little is known about the effects of MYPT1 in gastric cancer (GC). MATERIAL AND METHODS In our study, MYPT1 expression was detected by quantitative real-time reverse transcription PCR (qRT-PCR) in GC tissues, different advanced pathological stages of GC tissues, and preoperative and postoperative patients. Kaplan-Meier analysis was used to measure the overall survival of GC patients. MYPT1 expression was analyzed by qRT-PCR and Western blot assays in GES-1 cells and GC cells. Cell proliferation, cycle, and migration and invasion abilities were detected by CCK-8, flow cytometry, and Transwell assays. E-cadherin, TIMP-2, MMP-2, MMP-9 RhoA, and p-RhoA expressions were assessed by qRT-PCR and Western blot assays in treated SNU-5 cells. RESULTS Our results indicated that MYPT1 was down-regulated in GC tissues and cells, and is related to clinical stages and overall survival of GC. Functional research demonstrated that overexpression of MYPT1 can inhibit cell proliferation, cell cycle progression, and migration and invasion of GC cells. Many studies on mechanisms reported that overexpression of MYPT1 dramatically improved the expression levels of cell cycle-related genes (Cyclin D1 and c-myc), significantly increased epithelial marker (E-cadherin) expression, and decreased invasion-associated genes (TIMP-2 and MMP-2) expressions in SNU-5 cells. In addition, we found that MYPT1 suppressed RhoA phosphorylation. CONCLUSIONS We verified that MYPT1 inhibits GC cell proliferation and metastasis by regulating RhoA phosphorylation.

Zhong X, Lee HN, Surh YJ
RvD1 inhibits TNFα-induced c-Myc expression in normal intestinal epithelial cells and destabilizes hyper-expressed c-Myc in colon cancer cells.
Biochem Biophys Res Commun. 2018; 496(2):316-323 [PubMed] Related Publications
Inflammatory bowel diseases, including ulcerative colitis and Crohn's disease, are persistent disorders that lead to development of colitis-associated cancer (CAC). Facilitated resolution of colitis has been addressed as a novel therapeutic strategy to control development of CAC. Resolvin D1 (RvD1) is an endogenous lipid mediator that is generated from docosahexaenoic acid during the resolution of inflammation. Although the pro-resolving effects of RvDs have been extensively investigated and well defined, the role for RvD1 in CAC remains largely unknown. In this study, we found that RvD1 inhibited the expression of c-Myc in normal colon cells stimulated with tumor necrosis factor-α (TNFα) and also in colon cancer cells. The suppression of TNFα-induced upregulation of c-Myc in normal cells was mediated through attenuation of NF-κB signaling. Notably, RvD1 destabilized the constitutively overexpressed c-Myc protein in HCT 116 human colon cancer cells by stimulating its ubiquitination and subsequent proteasomal degradation. Further, we revealed that RvD1 stimulated c-Myc degradation through direct interaction with the ALX/FPR2 receptor. This interaction resulted in inhibition of activation of extracellular signal-regulated kinase, thereby attenuating phosphorylation-dependent stabilization of c-Myc.

Ivanov AA, Gonzalez-Pecchi V, Khuri LF, et al.
OncoPPi-informed discovery of mitogen-activated protein kinase kinase 3 as a novel binding partner of c-Myc.
Oncogene. 2017; 36(42):5852-5860 [PubMed] Free Access to Full Article Related Publications
Mitogen-activated protein kinase kinase 3 (MKK3) is a dual threonine/tyrosine protein kinase that regulates inflammation, proliferation and apoptosis through specific phosphorylation and activation of the p38 mitogen-activated protein kinase. However, the role of MKK3 beyond p38-signaling remains elusive. Recently, we reported a protein-protein interaction (PPI) network of cancer-associated genes, termed OncoPPi, as a resource for the scientific community to generate new biological models. Analysis of the OncoPPi connectivity identified MKK3 as one of the major hub proteins in the network. Here, we show that MKK3 interacts with a large number of proteins critical for cell growth and metabolism, including the major oncogenic driver MYC. Multiple complementary approaches were used to demonstrate the direct interaction of MKK3 with MYC in vitro and in vivo. Computational modeling and experimental studies mapped the interaction interface to the MYC helix-loop-helix domain and a novel 15-residue MYC-binding motif in MKK3 (MBM). The MBM in MKK3 is distinct from the known binding sites for p38 or upstream kinases. Functionally, MKK3 stabilized MYC protein, enhanced its transcriptional activity and increased expression of MYC-regulated genes. The defined MBM peptide mimicked the MKK3 effect in promoting MYC activity. Together, the exploration of OncoPPi led to a new biological model in which MKK3 operates by two distinct mechanisms in cellular regulation through its phosphorylation of p38 and its activation of MYC through PPI.

Li J, Liang Y, Lv H, et al.
miR-26a and miR-26b inhibit esophageal squamous cancer cell proliferation through suppression of c-MYC pathway.
Gene. 2017; 625:1-9 [PubMed] Related Publications
Dysregulation of c-Myc is one of the most common abnormalities in human malignancies, including esophageal cancer, one of the world's most lethal cancers. MicroRNA-26 family, including miR-26a and miR-26b, is transcriptionally suppressed by c-MYC. Our previous microarray data indicated a decreased-expression of miR-26 family in esophageal squamous cell carcinoma (ESCC). However, its roles in c-MYC pathway regulation and esophageal cancer tumorigenesis have yet not been elucidated. In this study, we expanded the detection of miR-26 expression in ESCC patients and found that the great majority of ESCC tissues showed an >50% reduction, even in the early-staged tumor. Furthermore, ectopic expression of miR-26a or miR-26b induced ESCC cell growth inhibition and G1 phase arrest. MYC binding protein (MYCBP) was identified as a direct target of miR-26. MiR-26 could dramatically decrease MYCBP mRNA and protein levels, as well as the expression of luciferase carrying MYCBP 3'-untranslated region. Moreover, knock-down of MYCBP mimicked the effect of miR-26. More importantly, miR-26 overexpression could downregulate a series of c-MYC target genes as MYCBP silence did. Taken together, these results indicate that miR-26 family can suppress esophageal cancer cell proliferation by inhibition of MYCBP, subsequently downregulate c-MYC pathway. Besides, we also found that reduction of miR-26 expression in ESCC was not due to DNA methylation. Hence, our study reveals a novel feedback loop for c-MYC pathway and implicates miR-26 as a potential target for prevention and treatment of esophageal cancer.

Lu M, Chen WH, Wang CY, et al.
Reciprocal regulation of miR-1254 and c-Myc in oral squamous cell carcinoma suppresses EMT-mediated metastasis and tumor-initiating properties through MAPK signaling.
Biochem Biophys Res Commun. 2017; 484(4):801-807 [PubMed] Related Publications
AIM: This study aimed to determine the effect of miR-1254 on oral squamous cell carcinoma (OSCC) metastasis and the specific mechanism involved.
METHODS: The metastatic properties of OSCC cells were analyzed by transwell assays. The tumor-initiating properties of OSCC cells were analyzed by tumor sphere formation assays. The mRNA and protein expressions of targeted genes were determined by quantitative polymerase chain reaction assays and western blot analyses, respectively. Xenograft experiments were employed to evaluate the anti-metastatic effects of miR-1254 and miR-1254-mediated cancer stem cell (CSC) properties in vivo. The gene targets of miR-1254 were investigated by luciferase reporter assays. Chromatin immunoprecipitation assays were performed to observe the transcriptional regulation of miR-1254 biogenesis by transcription factor.
RESULTS: miR-1254 attenuated OSCC metastasis and tumor-initiating properties in vitro and in vivo. Consistent with the experimental observations, miR-1254 was decreased in late-stage OSCCs and strongly correlated with risk of OSCC metastasis. Moreover, miR-1254 was mechanistically shown to down-regulate MAP3K3, accompanied by inactivation of the MAPK signaling pathway and inhibition of epithelial-mesenchymal transition (EMT) in OSCC cells. miR-1254 was transcriptionally repressed by c-Myc to form a positive feed back loop through MAPK signaling.
CONCLUSION: Our findings suggest that miR-1254 is a potential target for the treatment of OSCCs, and miR-1254 can be clinically utilized as a biomarker for the clinical prognosis or diagnosis of OSCCs.

Kikuchi A, Suzuki T, Nakazawa T, et al.
ASP5878, a selective FGFR inhibitor, to treat FGFR3-dependent urothelial cancer with or without chemoresistance.
Cancer Sci. 2017; 108(2):236-242 [PubMed] Free Access to Full Article Related Publications
FGF/FGFR gene aberrations such as amplification, mutation and fusion are associated with many types of human cancers including urothelial cancer. FGFR kinase inhibitors are expected to be a targeted therapy for urothelial cancer harboring FGFR3 gene alternations. ASP5878, a selective inhibitor of FGFR1, 2, 3 and 4 under clinical investigation, selectively inhibited cell proliferation of urothelial cancer cell lines harboring FGFR3 point mutation or fusion (UM-UC-14, RT-112, RT4 and SW 780) among 23 urothelial cancer cell lines. Furthermore, ASP5878 inhibited cell proliferation of adriamycin-resistant UM-UC-14 cell line harboring MDR1 overexpression and gemcitabine-resistant RT-112 cell line. The protein expression of c-MYC, an oncoprotein, in gemcitabine-resistant RT-112 cell line was higher than that in RT-112 parental cell line and ASP5878 decreased the c-MYC expression in both RT-112 parental and gemcitabine-resistant RT-112 cell lines. Once-daily oral administration of ASP5878 exerted potent antitumor activities in UM-UC-14, RT-112 and gemcitabine-resistant RT-112 xenograft models without affecting body weight. These findings suggest that ASP5878 has the potential to be an oral targeted therapy against urothelial cancer harboring FGFR3 fusion or FGFR3 point mutation after the acquisition of gemcitabine- or adriamycin-resistance.

Jiang X, Hu C, Arnovitz S, et al.
miR-22 has a potent anti-tumour role with therapeutic potential in acute myeloid leukaemia.
Nat Commun. 2016; 7:11452 [PubMed] Free Access to Full Article Related Publications
MicroRNAs are subject to precise regulation and have key roles in tumorigenesis. In contrast to the oncogenic role of miR-22 reported in myelodysplastic syndrome (MDS) and breast cancer, here we show that miR-22 is an essential anti-tumour gatekeeper in de novo acute myeloid leukaemia (AML) where it is significantly downregulated. Forced expression of miR-22 significantly suppresses leukaemic cell viability and growth in vitro, and substantially inhibits leukaemia development and maintenance in vivo. Mechanistically, miR-22 targets multiple oncogenes, including CRTC1, FLT3 and MYCBP, and thus represses the CREB and MYC pathways. The downregulation of miR-22 in AML is caused by TET1/GFI1/EZH2/SIN3A-mediated epigenetic repression and/or DNA copy-number loss. Furthermore, nanoparticles carrying miR-22 oligos significantly inhibit leukaemia progression in vivo. Together, our study uncovers a TET1/GFI1/EZH2/SIN3A/miR-22/CREB-MYC signalling circuit and thereby provides insights into epigenetic/genetic mechanisms underlying the pathogenesis of AML, and also highlights the clinical potential of miR-22-based AML therapy.

Wang H, Yan X, Ji LY, et al.
miR-139 Functions as An Antioncomir to Repress Glioma Progression Through Targeting IGF-1 R, AMY-1, and PGC-1β.
Technol Cancer Res Treat. 2017; 16(4):497-511 [PubMed] Free Access to Full Article Related Publications
Gliomas are the most common primary malignant brain tumor with poor prognosis, characterized by a highly heterogeneous cell population, extensive proliferation, and migration. A lot of molecular mechanisms regulate gliomas development and invasion, including abnormal expression of oncogenes and variation of epigenetic modification. MicroRNAs could affect cell growth and functions. Several reports have demonstrated that miR-139 plays multifunctions in kinds of solid tumors through different pathways. However, the antitumor mechanisms of this miR-139 are not unveiled in detail. In this study, we not only validated the low expression level of miR-139 in glioma tissues and cell lines but also detected the effect of miR-139 on modulating gliomas proliferation and invasion both in vitro and in vivo. We identified insulin-like growth factor 1 receptor, associate of Myc 1, and peroxisome proliferator-activated receptor γ coactivator 1β as direct targets of miR-139 and the levels of them were all inversely correlated with miR-139 in gliomas. Insulin like growth factor 1 receptor promoted gliomas invasion through Akt signaling and increased proliferation in the peroxisome proliferator-activated receptor γ coactivator 1β-dependent way. Associate of Myc 1 also facilitated gliomas progression by activating c-Myc pathway. Overexpression of the target genes could retrieve the antitumor function of miR-139, respectively, in different degrees. The nude mice transplantation tumor experiment displayed that glioma cells stably expressed miR-139 growth much slower in vivo than the negative control cells. Taken together, these findings suggested miR-139 acted as a favorable factor against gliomas progression and uncovered a novel regulatory mechanism, which may provide a new evidenced prognostic marker and therapeutic target for gliomas.

Tidwell WJ, Haq J, Kozlowski KF, Googe PB
C-MYC positive angiosarcoma of skin and breast following MammoSite® treatment.
Dermatol Online J. 2015; 21(10) [PubMed] Related Publications
Angiosarcoma of the skin and breast is a known complication of chronic lymphedema following mastectomy or external radiation therapy for breast cancer. We report a 68-year-old woman who presented with a 2.5 cm violaceous plaque on the skin of the right breast and a 3 cm mixed mass of the same breast by ultrasound 9 years after MammoSite® balloon brachytherapy.  Biopsy of the skin lesion and the breast mass showed an infiltrating high grade angiosarcoma.  The tumor cells in the skin and breast showed immunohistochemical reactivity for C-MYC.  A total mastectomy confirmed the presence of high grade angiosarcoma in the skin and parenchyma of the breast and radiation changes in the breast parenchyma.  Surgical margins were considered negative.  The patient had cutaneous recurrence of angiosarcoma three months after the mastectomy.  There have been only two other case reports in the literature of angiosarcoma on the skin following MammoSite® therapy. The c-myc mutation has been shown to be a specific mutation for angiosarcoma following radiation treatment. It is not found in atypical vascular lesions following irradiation or angiosarcoma unrelated to radiation treatment.

Cheng J, Lv Z, Weng X, et al.
Hsp27 Acts as a Master Molecular Chaperone and Plays an Essential Role in Hepatocellular Carcinoma Progression.
Digestion. 2015; 92(4):192-202 [PubMed] Related Publications
AIMS: Hsp27, a master molecular chaperone, plays an important role in cancer. However, the specific co-chaperones that partner with Hsp27 and the role of Hsp27 in hepatocellular carcinoma (HCC) are not fully enumerated. The present study focuses on the role of Hsp27 in HCC and explores its potential co-chaperones in HCC development.
METHODS: Gene overexpression or knockdown was used to observe the role of Hsp27 in HCC. Co-immunoprecipitation and mass spectrometry were used to explore apoptosis resistance by regulating multiple co-chaperones of Hsp27. Hsp27 protein-protein interaction (PPI) networks were constructed by the MetaCore software.
RESULTS: Hsp27 was upregulated in HCC tissues, and Hsp27 overexpression significantly facilitated formation of HCC cell colony and invasion in normoxia and tolerance in hypoxia by interacting with HIF-1α. Next, the analysis of microarrays revealed that Hsp27 regulated several cellular signaling pathways, including Wnt, ErbB and TGF-β signaling. Moreover, we characterized the Hsp27 PPI map, which indicated that Hsp27 along with its co-chaperones formed different complexes and exerts transcription regulation activity by activating sp1, c-Myc, p53 and ESR1.
CONCLUSIONS: Hsp27 along with its co-chaperones was related to the development of HCC by regulating multiple signaling pathways, and drugs that target Hsp27 along with its co-chaperones may be a potential therapy for HCC.

Sibbesen NA, Kopp KL, Litvinov IV, et al.
Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma.
Oncotarget. 2015; 6(24):20555-69 [PubMed] Free Access to Full Article Related Publications
Aberrant activation of Janus kinase-3 (Jak3) and its key down-stream effectors, Signal Transducer and Activator of Transcription-3 (STAT3) and STAT5, is a key feature of malignant transformation in cutaneous T-cell lymphoma (CTCL). However, it remains only partially understood how Jak3/STAT activation promotes lymphomagenesis. Recently, non-coding microRNAs (miRNAs) have been implicated in the pathogenesis of this malignancy. Here, we show that (i) malignant T cells display a decreased expression of a tumor suppressor miRNA, miR-22, when compared to non-malignant T cells, (ii) STAT5 binds the promoter of the miR-22 host gene, and (iii) inhibition of Jak3, STAT3, and STAT5 triggers increased expression of pri-miR-22 and miR-22. Curcumin, a nutrient with anti-Jak3 activity and histone deacetylase inhibitors (HDACi) also trigger increased expression of pri-miR-22 and miR-22. Transfection of malignant T cells with recombinant miR-22 inhibits the expression of validated miR-22 targets including NCoA1, a transcriptional co-activator in others cancers, as well as HDAC6, MAX, MYCBP, PTEN, and CDK2, which have all been implicated in CTCL pathogenesis. In conclusion, we provide the first evidence that de-regulated Jak3/STAT3/STAT5 signalling in CTCL cells represses the expression of the gene encoding miR-22, a novel tumor suppressor miRNA.

Ariga H
Common mechanisms of onset of cancer and neurodegenerative diseases.
Biol Pharm Bull. 2015; 38(6):795-808 [PubMed] Related Publications
Onset of cancer and neurodegenerative disease occurs by abnormal cell growth and neuronal cell death, respectively, and the number of patients with both diseases has been increasing in parallel with an increase in mean lifetime, especially in developed countries. Although both diseases are sporadic, about 10% of the diseases are genetically inherited, and analyses of such familial forms of gene products have contributed to an understanding of the molecular mechanisms underlying the onset and pathogenesis of these diseases. I have been working on c-myc, a protooncogene, for a long time and identified various c-Myc-binding proteins that play roles in c-Myc-derived tumorigenesis. Among these proteins, some proteins have been found to be also responsible for the onset of neurodegenerative diseases, including Parkinson's disease, retinitis pigmentosa and cerebellar atrophy. In this review, I summarize our findings indicating the common mechanisms of onset between cancer and neurodegenerative diseases, with a focus on genes such as DJ-1 and Myc-Modulator 1 (MM-1) and signaling pathways that contribute to the onset and pathogenesis of cancer and neurodegenerative diseases.

Zhang W, Wang YE, Zhang Y, et al.
Global epigenetic regulation of microRNAs in multiple myeloma.
PLoS One. 2014; 9(10):e110973 [PubMed] Free Access to Full Article Related Publications
Epigenetic changes frequently occur during tumorigenesis and DNA hypermethylation may account for the inactivation of tumor suppressor genes in cancer cells. Studies in Multiple Myeloma (MM) have shown variable DNA methylation patterns with focal hypermethylation changes in clinically aggressive subtypes. We studied global methylation patterns in patients with relapsed/refractory MM and found that the majority of methylation peaks were located in the intronic and intragenic regions in MM samples. Therefore, we investigated the effect of methylation on miRNA regulation in MM. To date, the mechanism by which global miRNA suppression occurs in MM has not been fully described. In this study, we report hypermethylation of miRNAs in MM and perform confirmation in MM cell lines using bisulfite sequencing and methylation-specific PCR (MSP) in the presence or absence of the DNA demethylating agent 5-aza-2'-deoxycytidine. We further characterized the hypermethylation-dependent inhibition of miR-152, -10b-5p and -34c-3p which was shown to exert a putative tumor suppressive role in MM. These findings were corroborated by the demonstration that the same miRNAs were down-regulated in MM patients compared to healthy individuals, alongside enrichment of miR-152-, -10b-5p, and miR-34c-3p-predicted targets, as shown at the mRNA level in primary MM cells. Demethylation or gain of function studies of these specific miRNAs led to induction of apoptosis and inhibition of proliferation as well as down-regulation of putative oncogene targets of these miRNAs such as DNMT1, E2F3, BTRC and MYCBP. These findings provide the rationale for epigenetic therapeutic approaches in subgroups of MM.

Jeon HM, Kim DH, Jung WH, Koo JS
Expression of cell metabolism-related genes in different molecular subtypes of triple-negative breast cancer.
Tumori. 2013 Jul-Aug; 99(4):555-64 [PubMed] Related Publications
AIMS AND BACKGROUND: We evaluated the difference in and significance of cancer cell metabolism by molecular subtyping of triple-negative breast carcinoma.
METHODS: Tissue microarrays from 122 surgical specimens of triple-negative breast carcinoma patients and immunohistochemical staining for CK5/6, epidermal growth factor receptor, claudin 3, claudin 4, claudin 7, E-cadherin, androgen receptor, and gamma-glutamyltransferase 1 were used to classify triple-negative breast carcinoma as follows: basal-like type, molecular apocrine type, claudin low type, mixed type and null type. In addition, immunohistochemical staining for metabolism-related proteins such as c-myc, insulin-like growth factor (g)-1, hypoxia-inducible factor 1-1α, glucose transporter 1, carbonic anhydrase IX antibody, macrophage migration inhibitory factor, and pyruvate dehydrogenase kinase 1 was used to compare the differences according to molecular subtype and clinicopathological factors.
RESULTS: The basal-like type showed the highest proportion of high glucose transporter 1 expression (P = 0.049) and carbonic anhydrase IX antibody expression (P = 0.008). Hypoxia-inducible factor 1-1α expression was associated with lymph node metastasis (P = 0.001) and central fibrotic zone (P = 0.012), and high glucose transporter 1 expression was related to high histologic grade (P = 0.007), cytokeratin 5/6 positivity (P = 0.002), and central fibrotic zone (P = 0.017). Finally, carbonic anhydrase IX antibody was associated with cytokeratin 5/6 positivity (P = 0.001) and central fibrotic zone (P = 0.048).
CONCLUSIONS: Our study revealed the different characteristics of cancer cell metabolism according to the molecular subtypes of triple-negative breast carcinoma. Among them, basal-like type was the most glycolytic and acid-resistant phenotype.

Sayed-Ahmed MM, Hafez MM, Al-Shabanah OA, et al.
Increased expression of biological markers as potential therapeutic targets in Saudi women with triple-negative breast cancer.
Tumori. 2013 Jul-Aug; 99(4):545-54 [PubMed] Related Publications
AIMS AND BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks the expression of hormone receptors and human epidermal growth factor receptor 2 (HER2). Although TNBC represents only 15% of all types of breast cancer, it accounts for a large number of metastatic cases and deaths. Because of the high metastatic rate and both local and systemic recurrence associated with TNBC, extensive research efforts are actively looking for target therapies to effectively treat this aggressive disease. Accordingly, this study has been initiated to investigate the differential expression of biological markers in TNBC and non-TNBC Saudi women that might be utilized as potential targeted therapy and/or predict the sensitivity to currently available therapeutic regimens.
METHODS AND STUDY DESIGN: Two hundred formalin-fixed, paraffin-embedded (FFPE) breast cancer tissues were selected and divided into 3 groups: benign breast tissues (20), TNBC tissues (80) and non-TNBC tissues (100). Expression of mRNA in FFPE tissues was analyzed using real-time polymerase chain reaction (RT-PCR) for the following genes: poly (ADP-ribose) polymerase 1 (PARP-1), topoisomerase 2A (TOPO-2A), vascular endothelial growth factor (VEGF), C-MYC, basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMP-2 and MMP-9), human epidermal growth factor 1 (HER1) and multidrug resistance (MDR) genes.
RESULTS: In the TNBC group, expression of PARP-1, TOPO-2A, HER1, C-MYC, VEGF, bFGF and MMP-2 showed a highly significant increase compared to the non-TNBC group.
CONCLUSIONS: The results of this study suggest that (1) TNBC patients will benefit more from TOPO-2A inhibitors as well as antiangiogenic and antimetastatic therapies; (2) inhibition of these target genes is emerging as one of the most exciting and promising targeted therapeutic strategies to treat TNBC in which the intended targets are DNA repair, tumor angiogenesis and metastasis.

Crowder SW, Horton LW, Lee SH, et al.
Passage-dependent cancerous transformation of human mesenchymal stem cells under carcinogenic hypoxia.
FASEB J. 2013; 27(7):2788-98 [PubMed] Free Access to Full Article Related Publications
Bone marrow-derived human mesenchymal stem cells (hMSCs) either promote or inhibit cancer progression, depending on factors that heretofore have been undefined. Here we have utilized extreme hypoxia (0.5% O2) and concurrent treatment with metal carcinogen (nickel) to evaluate the passage-dependent response of hMSCs toward cancerous transformation. Effects of hypoxia and nickel treatment on hMSC proliferation, apoptosis, gene and protein expression, replicative senescence, reactive oxygen species (ROS), redox mechanisms, and in vivo tumor growth were analyzed. The behavior of late passage hMSCs in a carcinogenic hypoxia environment follows a profile similar to that of transformed cancer cells (i.e., increased expression of oncogenic proteins, decreased expression of tumor suppressor protein, increased proliferation, decreased apoptosis, and aberrant redox mechanisms), but this effect was not observed in earlier passage control cells. These events resulted in accumulated intracellular ROS in vitro and excessive proliferation in vivo. We suggest a mechanism by which carcinogenic hypoxia modulates the activity of three critical transcription factors (c-MYC, p53, and HIF1), resulting in accumulated ROS and causing hMSCs to undergo cancer-like behavioral changes. This is the first study to utilize carcinogenic hypoxia as an environmentally relevant experimental model for studying the age-dependent cancerous transformation of hMSCs.

Song YH, Jeong SJ, Kwon HY, et al.
Ursolic acid from Oldenlandia diffusa induces apoptosis via activation of caspases and phosphorylation of glycogen synthase kinase 3 beta in SK-OV-3 ovarian cancer cells.
Biol Pharm Bull. 2012; 35(7):1022-8 [PubMed] Related Publications
Although ursolic acid isolated from Oldenlandia diffusa (Rubiaceae) was known to have anticancer activities in prostate, breast and liver cancers, the underlying mechanism of ursolic acid in ovarian cancer cells was not investigated so far. In the present study, the apoptotic mechanism of ursolic acid was elucidated in SK-OV-3 ovarian cancer cells by 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay, cell cycle analysis and Western blotting. Ursolic acid exerted cytotoxicity against SK-OV-3 and A2780 ovarian cancer cells with IC₅₀ of ca. 50 and 65 µM, respectively. Apoptotic bodies were observed in ursolic acid treated SK-OV-3 cells. Also, ursolic acid significantly increased ethidium homodimer stained cells and sub-G1 apoptotic portion in SK-OV-3 cells. Consistently, Western blotting revealed that ursolic acid effectively cleaved poly(ADP-ribose) polymerase (PARP), caspase-9 and -3, suppressed the expression of survival genes such as c-Myc, Bcl-x(L) and astrocyte elevated gene (AEG)-1, and upregulated phosphorylation of extracellular signal-regulated kinase (ERK) in SK-OV-3 cells. Interestingly, ursolic acid suppressed β-catenin degradation as well as enhanced phosphorylation of glycogen synthase kinase 3 beta (GSK 3β). Furthermore, GSK 3β inhibitor SB216763 blocked the cleavages of caspase-3 and PARP induced by ursolic acid and proteosomal inhibitor MG132 disturbed down-regulation of β-catenin, activation of caspase-3 and decreased mitochondrial membrane potential (MMP) induced by ursolic acid in SK-OV-3 cells. Overall, our findings suggest that ursolic acid induces apoptosis via activation of caspase and phosphorylation of GSK 3β in SK-OV-3 cancer cells as a potent anti-cancer agent for ovarian cancer therapy.

Ryan SL, Schwalbe EC, Cole M, et al.
MYC family amplification and clinical risk-factors interact to predict an extremely poor prognosis in childhood medulloblastoma.
Acta Neuropathol. 2012; 123(4):501-13 [PubMed] Related Publications
The MYC oncogenes are the most commonly amplified loci in medulloblastoma, and have previously been proposed as biomarkers of adverse disease prognosis by us and others. Here, we report focussed and comprehensive investigations of MYCC, MYCN and MYCL in an extensive medulloblastoma cohort (n = 292), aimed to define more precisely their biological significance and optimal clinical application to direct improved disease risk-stratification and individualisation of therapy. MYCC and MYCN expression elevations were multifactorial, associated with high-risk (gene amplification, large-cell/anaplastic pathology (LCA)) and favourable-risk (WNT/SHH molecular subgroups) disease features. Highly variable cellular gene amplification patterns underlay overall MYC copy number elevations observed in tumour biopsies; we used these alternative measures together to define quantitative methodologies and thresholds for amplification detection in routinely collected tumour material. MYCC and MYCN amplification, but not gain, each had independent prognostic significance in non-infants (≥3.0-16.0 years), but MYCC conferred a greater hazard to survival than MYCN when considered across this treatment group. MYCN's weaker group-wide survival relationship may be explained by its pleiotropic behaviour between clinical disease-risk groups; MYCN predicted poor prognosis in clinical high-risk (metastatic (M+) or LCA), but not standard-risk, patients. Extending these findings, survival decreased in proportion to the total number of independently significant high-risk features present (LCA, M+ or MYCC/MYCN amplification). This cumulative-risk model defines a patient group characterised by ≥2 independent risk-factors and an extremely poor prognosis (<15% survival), which can be identified straightforwardly using the reported MYC amplification detection methodologies alongside clinical assessments, enabling targeting for novel/intensified therapies in future clinical studies.

Díaz-Molina JP, Llorente JL, Vivanco B, et al.
Wnt-pathway activation in intestinal-type sinonasal adenocarcinoma.
Rhinology. 2011; 49(5):593-9 [PubMed] Related Publications
BACKGROUND: Intestinal-type sinonasal adenocarcinoma (ITAC) is an epithelial cancer of the sinonasal sinuses that shows histological similarity to colorectal cancer (CRC) and share chronic inflammation as a possible etiological factor. The Wnt-pathway is one of the most important tumourigenic pathways in CRC. The aim of this study was to investigate if the Wnt-pathway is activated in ITAC.
METHODOLOGY: Protein expression profiles of E-cadherin, β-catenin, c-myc and cyclin D1 were analysed by immunohistochemistry in 83 samples of ITAC, organized into tissue microarray blocks.
RESULTS: Nuclear β-catenin expression was observed in 31% of the cases and was twice as frequent in papillary/colonic ITAC compared to solid/mucinous subtypes. Loss of membranous β-catenin staining occurred in 24% and loss of membranous E-cadherin in 6% of the cases and this was more prominent in mucinous types. Strong c-myc and cyclin D1 expression was observed in 30% and 4% of the cases, respectively. Nuclear β-catenin expression was significantly related to poor clinical outcome, independent from established factors as tumour stage and histological type.
CONCLUSION: The presence of nuclear β-catenin in 31% of patients with ITACs indicated that in a subset of patients, the Wnt-pathway is active and conveys a worse prognosis.

Bayley JP, Devilee P
The Warburg effect in 2012.
Curr Opin Oncol. 2012; 24(1):62-7 [PubMed] Related Publications
PURPOSE OF REVIEW: A revival of interest in tumor metabolism is underway and here we discuss recent results with a focus on the central theme of the Warburg effect, aerobic glycolysis.
RECENT FINDINGS: The M2 tumor-specific isoform of pyruvate kinase has generated much interest, but it has now been reported that PKM2 is not specific to tumors. Despite this setback, the reciprocal regulation of PKM2, prolyl hydroxylase 3 and HIF-1 in a positive feedback loop shows that PKM2 is important to tumor metabolism. Hexokinase II was reported to be a crucial regulator of glycolysis in glioblastoma multiforme, and the importance of lactate dehydrogenase was underlined by evidence that a 'lactate-based dialog' exists between cancer cells and endothelial cells. A growing appreciation of the role of oncogenes and tumor suppressor genes in the Warburg effect was reflected in reports of the regulation of glutamine metabolism by p53, the role of c-Myc in the high glucose uptake of tumors, and the regulation of ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5) and ATP consumption by AKT. The sirtuins, SIRT3 and SIRT6, were also shown to play central roles in aerobic glycolysis and other aspects of tumor metabolism.
SUMMARY: The results discussed illustrate the growing integration of the previously distinct fields of molecular biological and metabolic cancer research and show that this synergy is beginning to yield a more complete and comprehensive understanding of the tumor cell.

Möröy T, Saba I, Kosan C
The role of the transcription factor Miz-1 in lymphocyte development and lymphomagenesis-Binding Myc makes the difference.
Semin Immunol. 2011; 23(5):379-87 [PubMed] Related Publications
The Myc interacting zinc finger protein 1 (Miz-1) is a BTB/POZ domain containing transcription factor that can function as an activator or repressor depending on its binding partners. In a complex with co-factors such as nuclophosmin or p300, Miz-1 stimulates transcription of genes that encode regulators of cell cycle progression such as p21(Cip1) or p15(Ink4b) or inhibitors of apoptosis such as Bcl-2. In contrast, Miz-1 becomes a transcriptional repressor when it binds to c-Myc or Bcl-6, which replace nucleophosmin or p300. During lymphocyte development, Miz-1 functions as a regulator of the IL-7 signaling pathway at very early steps in the bone marrow and thymus. When the IL-7 receptor (IL-7R) recognizes its cognate cytokine, a cascade of events is initiated that involves the recruitment of janus kinases (JAK) to the cytoplasmic part of the IL-7R, the phosphorylation of Stat5, its dimerization and relocation to the nucleus, enabling a transcriptional programming that governs commitment, survival and proliferation of lymphoid lineage cells. Miz-1 is critical in this signal transduction pathway, since it controls the expression of Socs1, an inhibitor of JAKs and thus of Stat5 activation and Bcl-2 expression. A lack of Miz-1 blocks IL-7 mediated signaling, which is detrimental for early B- and T-lymphoid development. These functions of Miz-1 during early lymphocyte development are c-Myc-independent. In contrast, when c-Myc is constitutively over-expressed, for instance during c-Myc induced lymphomagenesis, the interaction between Miz-1 and c-Myc becomes important and critical for the initiation and maintenance of c-Myc-dependent lymphoid malignancies.

Mertz JA, Conery AR, Bryant BM, et al.
Targeting MYC dependence in cancer by inhibiting BET bromodomains.
Proc Natl Acad Sci U S A. 2011; 108(40):16669-74 [PubMed] Free Access to Full Article Related Publications
The MYC transcription factor is a master regulator of diverse cellular functions and has been long considered a compelling therapeutic target because of its role in a range of human malignancies. However, pharmacologic inhibition of MYC function has proven challenging because of both the diverse mechanisms driving its aberrant expression and the challenge of disrupting protein-DNA interactions. Here, we demonstrate the rapid and potent abrogation of MYC gene transcription by representative small molecule inhibitors of the BET family of chromatin adaptors. MYC transcriptional suppression was observed in the context of the natural, chromosomally translocated, and amplified gene locus. Inhibition of BET bromodomain-promoter interactions and subsequent reduction of MYC transcript and protein levels resulted in G(1) arrest and extensive apoptosis in a variety of leukemia and lymphoma cell lines. Exogenous expression of MYC from an artificial promoter that is resistant to BET regulation significantly protected cells from cell cycle arrest and growth suppression by BET inhibitors. MYC suppression was accompanied by deregulation of the MYC transcriptome, including potent reactivation of the p21 tumor suppressor. Treatment with a BET inhibitor resulted in significant antitumor activity in xenograft models of Burkitt's lymphoma and acute myeloid leukemia. These findings demonstrate that pharmacologic inhibition of MYC is achievable through targeting BET bromodomains. Such inhibitors may have clinical utility given the widespread pathogenetic role of MYC in cancer.

Zhu W, Cai MY, Tong ZT, et al.
Overexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymaltransition.
Gut. 2012; 61(4):562-75 [PubMed] Related Publications
BACKGROUND AND AIMS: The authors have previously isolated a putative oncogene, eukaryotic initiation factor 5A2 (EIF5A2) from 3q26. In this study, EIF5A2 was characterised for its role in colorectal carcinoma (CRC) aggressiveness and underlying molecular mechanisms.
METHODS: The expression dynamics of EIF5A2 were examined by immunohistochemistry in a cohort of carcinomatous and non-neoplastic colorectal tissues and cells. A series of in-vivo and in-vitro assays was performed to elucidate the function of EIF5A2 in CRC and its underlying mechanisms.
RESULTS: The overexpression of EIF5A2 was examined by immunohistochemistry in 102/229 (44.5%) CRC patients, and it was significantly correlated with tumour metastasis and determined to be an independent predictor of shortened survival (p<0.05). Ectopic overexpression of EIF5A2 in CRC cells enhanced cell motility and invasion in vitro and tumour metastasis in vivo, and induced epithelial-mesenchymal transition (EMT). The depletion of EIF5A2 expression prevented CRC cell invasiveness and inhibited EMT. Importantly, the metastasis-associated protein 1 (MTA1) gene was identified as a potential downstream target of EIF5A2 in CRC cells, and knockdown of MTA1 eliminated the augmentation of carcinoma cell migration, invasion and EMT by ectopic EIF5A2. The overexpression of EIF5A2 in CRC cells substantially enhanced the enrichment of c-myc on the promoter of MTA1, and MTA1 upregulation by EIF5A2 was partly dependent on c-myc.
CONCLUSION: The data suggest that EIF5A2 plays an important oncogenic role in CRC aggressiveness by the upregulation of MTA1 to induce EMT, and EIF5A2 could be employed as a novel prognostic marker and/or effective therapeutic target for CRC.

Wen G, Hong M, Li B, et al.
Transforming growth factor-β-induced protein (TGFBI) suppresses mesothelioma progression through the Akt/mTOR pathway.
Int J Oncol. 2011; 39(4):1001-9 [PubMed] Free Access to Full Article Related Publications
As an uncommon cancer, mesothelioma is very hard to treat with a low average survival rate owing to its usual late detection and being highly invasive. The link between asbestos exposure and the development of mesothelioma in humans is unequivocal. TGFBI, a secreted protein that is induced by transforming growth factor-β in various human cell types, has been shown to be associated with tumorigenesis in various types of tumors. It has been demonstrated that TGFBI expression is markedly suppressed in asbestos-induced tumorigenic cells, while an ectopic expression of TGFBI significantly suppresses tumorigenicity and progression in human bronchial epithelial cells. In order to delineate a potential role of TGFBI in mediating the molecular events that occur in mesothelioma tumorigenesis, we generated stable TGFBI knockdown mutants from the mesothelium cell line Met-5A by using an shRNA approach, and secondly created ectopic TGFBI overexpression mutants from the mesothelioma cell line H28 in which TGFBI is absent. We observed that in the absence of TGFBI, the knockdown mesothelial and mesothelioma cell lines exhibited an elevated proliferation rate, enhanced plating efficiency, increased anchorage-independent growth, as well as an increased cellular protein synthesis rate as compared with their respective controls. Furthermore, cell cycle regulatory proteins c-myc/cyclin D1/phosphor-Rb were upregulated; a more active PI3K/Akt/mTOR signaling pathway was also detected in TGFBI-depleted cell lines. These findings suggest that TGFBI may repress mesothelioma tumorigenesis and progression via the PI3K/Akt signaling pathway.

Sun T, Wang C, Xing J, Wu D
miR-429 modulates the expression of c-myc in human gastric carcinoma cells.
Eur J Cancer. 2011; 47(17):2552-9 [PubMed] Related Publications
AIM: MicroRNAs (miRNAs) are a recently discovered class of small non-coding RNAs that regulate gene expression and may contribute to the development and progression of many cancers. In this study, our goal was to investigate the regulation of miR-429 in gastric cancer and explored the mechanism/s by which it influenced pathogenesis of gastric cancer.
METHODS: We used real-time reverse transcriptase-polymerase chain reaction to quantify the expression level of miR-429 in 52 gastric cancer tissues and their paracancerous tissues. Bioinformatics was used to predict downstream target genes of miR-429. SGC-7901 gastric cancer cells were transfected with miR-429 mimics and endogenous c-myc expression was detected by western blots. We performed functional assays using the 3'UTR of the c-myc gene as a miR-429 target in a luciferase reporter assay system.
RESULTS: We showed that miR-429 was downregulated in human gastric carcinoma tissue and in SGC-7901 cells. Cell viability, proliferation and attachment were inhibited in miR-429-transfected cells. miR-429 significantly downregulated endogenous c-myc expression in SGC-7901 cells. Action of miR/429 on c-myc 3'UTR was confirmed. The levels of miR-429 in tumour tissue of patients with lymph node metastasis were significantly lower than in those without lymph node metastasis.
CONCLUSIONS: Our results suggested that miR-429 played a role in the pathogenesis of gastric carcinoma and may function as a recessive cancer gene. c-myc is an important miR-429 target gene.

Shaw EJ, Haylock B, Husband D, et al.
Gene expression in oligodendroglial tumors.
Cell Oncol (Dordr). 2011; 34(4):355-67 [PubMed] Related Publications
BACKGROUND: Oligodendroglial tumors with 1p/19q loss are more likely to be chemosensitive and have longer survival than those with intact 1p/19q, but not all respond to chemotherapy, warranting investigation of the biological basis of chemosensitivity.
METHODS: Gene expression profiling was performed using amplified antisense RNA from 28 oligodendroglial tumors treated with chemotherapy [26 serial stereotactic biopsy, 2 resection]. Expression of differentially expressed genes was validated by real-time PCR.
RESULTS: Unsupervised hierarchical clustering showed clustering of multiple samples from the same case in 14/17 cases and identified subgroups associated with tumor grade and 1p/19q status. 176 genes were differentially expressed, 164 being associated with 1p/19q loss (86% not on 1p or 19q). 94 genes differed between responders and non-responders to chemotherapy; 12 were not associated with 1p/19q loss. Significant differential expression was confirmed in 11/13 selected genes. Novel genes associated with response to therapy included SSBP2, GFRA1, FAP and RASD1. IQGAP1, INA, TGIF1, NR2F2 and MYCBP were differentially expressed in oligodendroglial tumors with 1p/19q loss.
CONCLUSION: Gene expression profiling using serial stereotactic biopsies indicated greater homogeneity within tumors than between tumors. Genes associated with 1p/19q status or response were identified warranting further elucidation of their role in oligodendroglial tumors.

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