Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MicroRNAs (miRNAs) are small, noncoding RNAs that can contribute to cancer development and progression by acting as oncogenes or tumor suppressor genes. Recent studies have also linked different sets of miRNAs to metastasis through either the promotion or suppression of this malignant process. Interestingly, epigenetic silencing of miRNAs with tumor suppressor features by CpG island hypermethylation is also emerging as a common hallmark of human tumors. Thus, we wondered whether there was a miRNA hypermethylation profile characteristic of human metastasis. We used a pharmacological and genomic approach to reveal this aberrant epigenetic silencing program by treating lymph node metastatic cancer cells with a DNA demethylating agent followed by hybridization to an expression microarray. Among the miRNAs that were reactivated upon drug treatment, miR-148a, miR-34b/c, and miR-9 were found to undergo specific hypermethylation-associated silencing in cancer cells compared with normal tissues. The reintroduction of miR-148a and miR-34b/c in cancer cells with epigenetic inactivation inhibited their motility, reduced tumor growth, and inhibited metastasis formation in xenograft models, with an associated down-regulation of the miRNA oncogenic target genes, such as C-MYC, E2F3, CDK6, and TGIF2. Most important, the involvement of miR-148a, miR-34b/c, and miR-9 hypermethylation in metastasis formation was also suggested in human primary malignancies (n = 207) because it was significantly associated with the appearance of lymph node metastasis. Our findings indicate that DNA methylation-associated silencing of tumor suppressor miRNAs contributes to the development of human cancer metastasis.
 ...
PMID:A microRNA DNA methylation signature for human cancer metastasis. 1908 43

Metastasis is a common feature in advanced cancers. To elucidate the mechanism underlying metastasis from analysis of primary disease would have substantial clinical benefit. MicroRNAs (miRNAs) have started a revolution in molecular biology, and emerged as key players in carcinogenesis. They have been identified in various tumor types, showing that different sets of miRNAs are usually deregulated in different cancers. Moreover, some miRNAs are aberrantly methylated and silenced, causing tumorigenesis. In the paper evaluated, the authors identified aberrantly methylated and silenced miRNAs that are cancer-specific using miRNA microarray techniques. Functional analyses for the selected genes proved that these miRNAs act on C-MYC, E2F3, CDK6 and TGIF2, resulting in metastasis through aberrant methylation of the miRNAs. These findings may have broad implications for mechanisms underlying metastasis in malignancies, and may be applicable to advance research in the clinical setting.
 ...
PMID:Identification of microRNAs caused by DNA methylation that induce metastasis. 1876 88