Research IndicatorsGraph generated 01 September 2019 using data from PubMed using criteria.
Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic. 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).
Numbers shown below represent number of publications held in OncomiRDB database for Oncogenic and Tumor-Suppressive MicroRNAs.
|Tissue||Target Gene(s)||Regulator(s)||MIR1258 Function in Cancer||Effect|
-non-small cell lung cancer (1)
|inhibit cell invasion (1)||tumor-suppressive
-breast cancer (1)
|HPSE (1)||inhibit cell invasion (1)|
reduce brain metastasis (1)
Source: OncomiRDB Wang D. et al. Bioinformatics 2014, 30(15):2237-2238.
miRBase, University of Manchester
Annotated database entry including the location and sequence of the mature miRNA sequence.
miRCancer, East Carolina University
Search miRCancer for miR-1258 associations with cancer and associated genes.
OMIM, Johns Hopkin University
Referenced article focusing on the relationship between phenotype and genotype.
International Cancer Genome Consortium.
Summary of gene and mutations by cancer type from ICGC
COSMIC, Sanger Institute
Somatic mutation information and related details
GEO Profiles, NCBI
Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus (GEO) repository.
Latest Publications: MIR1258 (cancer-related)
Loginov VI, Burdennyy AM, Filippova EA, et al.[Hypermethylation of miR-107, miR-130b, miR-203a, miR-1258 Genes Associated with Ovarian Cancer Development and Metastasis].
Mol Biol (Mosk). 2018 Sep-Oct; 52(5):801-809 [PubMed
] Related Publications
It is known that microRNAs (miRNAs) are able to dynamically regulate gene expression. At the same time, methylation can reduce expression of miRNA encoding genes and, therefore, reduce their inhibitory effects on mRNAs of target genes, including those of oncogenes, that promoting the development of tumors of different localization. The role of miRNA hypermethylation in the pathogenesis of ovarian cancer is not completely understood; so we conducted a search for new hypermethylated and potentially suppressor miRNA genes in ovarian tumors. Four new miRNA genes (MIR-107, MIR-130b, MIR-203a, MIR-1258) commonly hypermethylated (28-52%) in tumor tissues vs 4-7% in paired histologically normal tissues, p < 0.01, were identified in a representative set of 54 ovarian cancer samples using methylation-specific PCR. It was shown that hypermethylation of MIR-130b, MIR-203a, and MIR-1258 genes is significantly (p < 0.05) associated with metastasis of ovarian cancer. These results suggest the involvement of four miRNAs (miR-107, miR-130b, miR-203a, and miR-1258) and hypermethylation of their encoding genes in the pathogenesis of ovarian cancer.
Zhang Z, Li J, Huang Y, et al.Upregulated miR-1258 regulates cell cycle and inhibits cell proliferation by directly targeting E2F8 in CRC.
Cell Prolif. 2018; 51(6):e12505 [PubMed
] Related Publications
OBJECTIVES: MicroRNAs (miRNAs) as small noncoding RNA molecules function by regulating their target genes negatively. MiR-1258 was widely researched in multicancers, but its role remains unclear in colorectal cancer (CRC).
METHODS: The expression of miR-1258 and its specific target gene were detected in human CRC specimens and cell lines by miRNA RT-PCR, qRT-PCR and Western blot. The effects of miR-1258 on CRC proliferation were evaluated using CCK-8 assays, EdU incorporation, colony formation assays and cell-cycle assays; in vitro and the in vivo effects were investigated using a mouse tumorigenicity model. Luciferase reporter and RIP assays were employed to identify interactions between miR-1258 and its specific target gene.
RESULTS: MiR-1258 was downregulated in CRC tissues and CRC cell lines, and upregulated miR-1258 was proved to inhibit proliferation and arrest cell cycle at G0/G1 in vitro and vivo. Luciferase reporter, RIP and western blot assays revealed E2F8 to be a direct target of miR-1258. The effects of miR-1258 in proliferation and cell cycle regulation can be abolished by E2F8 through rescue experiments. By directly targeting E2F8, miR-1258 influenced the expression of several cell-cycle factors, including cyclin D1 (CCND1) and cyclin dependent kinase inhibitor 1A (p21).
CONCLUSION: MiR-1258 may function as a suppressive factor by negatively controlling E2F8, thus, highlighting the potential role of miR-1258 as a therapeutic target for human CRC.
Jiang W, Wei K, Pan C, et al.MicroRNA-1258 suppresses tumour progression via GRB2/Ras/Erk pathway in non-small-cell lung cancer.
Cell Prolif. 2018; 51(6):e12502 [PubMed
] Related Publications
OBJECTIVES: Lung cancer is still a disease with high morbidity and mortality in the world. MicroRNAs have been proven to act as an indispensable role in the reuse of multiple solid tumours. Although miR-1258 plays a vital role in suppressing metastasis in breast cancer and gastric cancer, the specific biological function of miR-1258 in non-small-cell lung cancer remains unclear.
METHODS: The differential expression of miR-1258 in NSCLC tissues and corresponding paracancerous tissues was detected by qRT-PCR and ISH. Flow cytometry and CCK-8, EdU, tubule formation, and senescence assays were performed, and xenograft models were studied to explore the function of miR-1258. Potential targets of miR-1258 were verified by dual luciferase reporter assay, qRT-PCR, IHC and Western blotting.
RESULTS: In vitro and in vivo gain- and loss-of-function assays suggested that miR-1258 inhibits NSCLC cell proliferation and induces senescence and apoptosis. The luciferase reporter assay, IHC and Western blotting analysis showed that GRB2 is one of the direct targets of miR-1258. The GRB2 overexpression plasmid can reverse the functional changes after overexpression of miR-1258. In contrast, miR-1258 inhibitor significantly reversed si-GRB2-induced GRB2 down-regulation. Mechanistically, overexpression of miR-1258 inhibits GRB2 expression and then leads to inactivation of the Ras/Erk oncogenic pathway.
CONCLUSIONS: Our results indicate that miR-1258 can suppress NSCLC progression by targeting the GRB2/Ras/Erk pathway, which may lead to different insights into potential biomarkers and novel therapeutic strategies for NSCLC patients.
Braga EA, Loginov VI, Burdennyi AM, et al.Five Hypermethylated MicroRNA Genes as Potential Markers of Ovarian Cancer.
Bull Exp Biol Med. 2018; 164(3):351-355 [PubMed
] Related Publications
MicroRNA and methylation are important epigenetic mechanisms in the pathogenesis of cancer. The role of a group of microRNA hypermethylated genes in the pathogenesis of ovarian cancer was studied and their diagnostic and prognostic potential was evaluated. Studies on a representative sample of 54 ovarian cancer specimens with the use of methyl-specific PCR resulted in detection of five microRNA genes (MIR-9-1, MIR-9-3, MIR-107, MIR-1258, and MIR-130b) methylated in the majority of tumor specimens in comparison with paired specimens of histologically intact tissue (37-57% vs. 4-9%, p<0.01). Methylation of three genes (MIR-9-1, MIR-9-3, and MIR-130b) was significantly (p≤0.05) associated with the parameters of ovarian cancer progress (clinical stage, differentiation degree, tumor size, and presence of metastases). These findings attest to oncosuppressive role of the studied microRNA genes (MIR-9-1, MIR-9-3, MIR-107, MIR-1258, and MIR-130b) in the pathogenesis and progress of ovarian cancer and indicated their prognostic potential.
Torres-Ferreira J, Ramalho-Carvalho J, Gomez A, et al.MiR-193b promoter methylation accurately detects prostate cancer in urine sediments and miR-34b/c or miR-129-2 promoter methylation define subsets of clinically aggressive tumors.
Mol Cancer. 2017; 16(1):26 [PubMed
] Free Access to Full Article Related Publications
BACKGROUND: Contemporary challenges of prostate cancer (PCa) include overdiagnosis and overtreatment, entailing the need for novel clinical tools to improve risk stratification and therapy selection. PCa diagnosis and prognostication might be perfected using epigenetic biomarkers, among which aberrant DNA methylation of microRNA promoters has not been systematically explored. Herein, we identified aberrantly methylated microRNAs promoters in PCa and assessed its diagnostic and prognostic biomarker potential.
METHODS: Using HumanMethylation450 BeadChip-based analysis differentially methylated CpGs in microRNA promoters were identified. Promoter methylation of six microRNAs (miR-34b/c, miR-129-2, miR-152, miR-193b, miR-663a and miR-1258) was analyzed by qMSP in three sets (180 prostatectomies, 95 urine sediments and 74 prostate biopsies). Biomarkers' diagnostic (validity estimates) and prognostic [disease-free (DFS) and disease-specific survival (DSS)] performance was assessed.
RESULTS: Significantly higher promoter methylation levels in PCa were confirmed for six candidate microRNAs. Except for miR-152, all displayed AUC values higher than 0.90, with miR-1258 and miR-193b disclosing the best performance (AUC = 0.99 and AUC = 0.96, respectively). In urine samples, miR-193b showed the best performance (91.6% sensitivity, 95.7% specificity, AUC = 0.96). Moreover, higher miR-129-2 independently predicted for shorter DSS and miR-34b/c methylation levels independently predicted for shorter DFS and DSS.
CONCLUSIONS: Quantitative miR-193b, miR-129-2 and miR-34b/c promoter methylation might be clinically useful PCa biomarkers for non-invasive detection/diagnosis and prognostication, both in tissue and urine samples.
Loginov VI, Burdennyy AM, Pronina IV, et al.[Novel miRNA genes hypermethylated in breast cancer].
Mol Biol (Mosk). 2016 Sep-Oct; 50(5):797-802 [PubMed
] Related Publications
MicroRNAs play an important role in the regulation of expression of many genes involved in cancer pathogenesis. One of the causes of miRNA level deregulation in tumors is the methylation of CpG islands in the promoter regions of the genes that encode them. Hypermethylation may lead to the suppression of miRNA gene expression and, as a consequence, to a decrease in their inhibitory effect on target gene mRNAs. A search for new miRNA genes hypermethylated in breast cancer has been carried out in the present study. The methylation of five miRNA genes associated with breast cancer (miR-132, miR-1258, miR-107, miR-130b, miR-137) has been as studied using a representative set of 41 breast cancer samples by methylation-specific PCR. Three new genes, MIR-132, MIR-137 and MIR-1258, with a high frequency of hypermethylation (41, 37 and 34%, respectively) have been identified in breast cancer. The methylation of these genes in the breast tissues of ten donors without cancer pathology in anamnesis was only found in single cases. These results enable the involvement of three miRNAs (miR-132, miR-137, miR-1258) and the methylation of the genes that encode them in the pathogenesis of breast cancer to be suggested.
Hepatocellular carcinoma (HCC) is the leading cause of cancer related death worldwide. The number of deaths is proportional to the global incidence, which highlights the aggressive tumor biology and lack of effective therapies. Dysregulation of microRNAs has been implicated in carcinogenesis and progression of liver cancer. Here, we identified that miR-1258 was significantly downregulated in HCC and associated with poor patients' survival. Overexpression of miR-1258 significantly inhibits liver cancer cell growth, proliferation and tumorigenicity through increasing cell cycle arrest in G0/G1 phase and promotes cell apoptosis. Interestingly, stable overexpression of miR-1258 suppresses cell migration, stemness and increases sensitivity of HCC cells to chemotherapy drug like doxorubicin. The CDC28 protein kinase regulatory subunit 1B (CKS1B) was identified as a functional downstream target of miR-1258. Re-expression of CKS1B overcomes miR-1258 induced apoptosis and increases stemness of HCC cells, suggesting that loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CKS1B . Therefore, loss of miR-1258 may be a potential diagnostic and prognostic biomarker and blocking miR-1258-CKS1B axis is a potential therapeutic strategy in HCC.
Rykov SV, Khodyrev DS, Pronina IV, et al.[Novel miRNA genes methylated in lung tumors].
Genetika. 2013; 49(7):896-901 [PubMed
] Related Publications
MicroRNAs play an important role in the regulation of expression of many genes and are involved in carcinogenesis. The regulation of miRNA gene expression can involve the methylation of promoter CpG islands. In this work, the methylation of six miRNA genes (mir-107, mir-125b-1, mir-130b, mir-137, mir-375, and mir-1258) in non-small-cell lung cancer (NSCLC) was studied for the first time by methylation-specific PCR using a representative set of specimens (39 cases). Four new genes (mir-125b-1, mir-137, mir-375, and mir-1258) methylated in primary NSCLC tumors were identified with frequencies of 56, 31, 56, and 36%, respectively. The frequencies of miRNA promoter methylation in DNA of tumors and histologically normal tissues differed significantly (P < or = 0.05 by Fisher's test). In lung tissues of 20 donors without a history of cancer, these genes were only methylated in a few cases. It was also shown that the previously unstudied promoter CpG islands of mir-107 and mir-130b were not methylated in NSCLC. The frequencies of mir-125b-1 and mir-137 methylation were shown for the first time to correlate with NSCLC progression (clinical stage and metastasis).
Tang D, Zhang Q, Zhao S, et al.The expression and clinical significance of microRNA-1258 and heparanase in human breast cancer.
Clin Biochem. 2013; 46(10-11):926-32 [PubMed
] Related Publications
OBJECTIVES: To investigate the expression profile of miR-1258 and heparanase (HPSE) in breast cancer and to assess their clinicopathological significance.
DESIGN AND METHODS: The expression levels of miR-1258 and HPSE were analyzed in normal, benign and malignant breast tissues. Their serum levels were evaluated in healthy women and in patients with benign and malignant breast disease. We studied the correlation between the expression of miR-1258 and HPSE and the clinical features presented by the patients.
RESULTS: MiR-1258 was down-regulated and HPSE was up-regulated in breast cancer, with a significant inverse correlation. A reduced miR-1258 expression and an elevated HPSE expression were associated with the lymph node status, late clinical stages, a short overall survival and a short relapse-free survival. In frozen fresh tissue samples, the miR-1258 levels in breast cancer with lymph node metastasis were significantly lower than that of breast cancer without lymph node metastasis and benign disease (BD). In contrast, the HPSE levels in breast cancer with lymph node metastasis were the highest. In serum samples, the miR-1258 levels in metastatic breast cancer (M1) were lower than that of primary breast cancer (M0) and BD. However, serum HPSE levels of M1 patients were significantly higher than that of M0 patients and BD patients.
CONCLUSIONS: MiR-1258 may play an important role in breast cancer development and progression by regulating the expression of HPSE, and they might be potential prognostic biomarkers for breast cancer.
Liu H, Chen X, Gao W, Jiang GThe expression of heparanase and microRNA-1258 in human non-small cell lung cancer.
Tumour Biol. 2012; 33(5):1327-34 [PubMed
] Related Publications
This study aims to discuss the correlation between miR-1258 and the expression of heparanase (HPSE) in the cancer cells of the patients with non-small cell lung cancer (NSCLC) and the inhibition mechanism of miR-1258 on the invasion of lung cancer cell. The expression level of miR-1258 was detected by TaqMan real-time PCR assay, the expression of HPSE was detected by immunohistochemistry, and the expression level of HPSE in the cancer tissue of each case was detected by western blot and in its adjacent tissue of 53 patients with NSCLC. The influence of miR-1258 on the invasion potential of the lung cancer cell line A549 was studied with lentivirus system including cloned miR-1258 fragments subsequently. The expression of HPSE and miR-1258 in NSCLC tissue was not obviously related to patient's gender, age, differentiation extent of cancer tissue, cancer types, etc., but also staging and lymph node metastasis, and the difference was significant. Further studies showed that the relationship between the expression level of miR-1258 and the expression of HPSE was closer. The relative expression level of miR-1258 was 0.58 ± 0.07 in HPSE positive sample and 1.58 ± 0.11 in HPSE negative sample, and the difference of which was notably significant (P < 0.0001). Western blot showed that the expression level of HPSE was highly negatively related to the expression level of miR-1258. The invasion potential of A549 was notably lowered when transfected by miR-1258. The miR-1258 regulates the expression level of HPSE to influence the morbidity and metastasis of NSCLC. The miR-1258 is likely to become the key to the treatment of lung cancer metastasis.
Heparanase (HPSE) is a potent protumorigenic, proangiogenic, and prometastatic enzyme that is overexpressed in brain metastatic breast cancer (BMBC). However, little is known about the regulation of this potential therapeutic target in BMBC, which remains very poorly managed in the clinic. We hypothesized that HPSE gene expression might be regulated by micro RNA that might be exploited therapeutically. Using miRanda and RNAhybrid, we identified miR-1258 as a candidate micro RNA that may directly target HPSE and suppress BMBC. In support of our hypothesis, we found that miR-1258 levels inversely correlated with heparanase expression, enzymatic activity, and cancer cell metastatic propensities, being lowest in highly aggressive BMBC cell variants compared with either nontumorigenic or nonmetastatic human mammary epithelial cells. These findings were validated by analyses of miR-1258 and heparanase content in paired clinical specimens of normal mammary gland versus invasive ductal carcinoma, and primary breast cancer versus BMBC. In regulatory experiments, miR-1258 inhibited the expression and activity of heparanase in BMBC cells, whereas modulating heparanase blocked the phenotypic effects of miR-1258. In functional experiments, stable expression of miR-1258 in BMBC cells inhibited heparanase in vitro cell invasion and experimental brain metastasis. Together, our findings illustrate how micro RNA mechanisms are linked to brain metastatic breast cancer through heparanase control, and they offer a strong rationale to develop heparanase-based therapeutics for treatment of cancer patients with brain metastases, BMBC in particular.