Identification of MicroRNAs Caused by DNA Methylation That Induce Metastasis

Makoto Suzuki, MD, PhD; Ichiro Yoshino, MD, PhD

Disclosures

Future Oncol. 2008;4(6):775-777. 

In This Article

Abstract and Introduction

Evaluation of: Lujambio A, Calin GA, Villanueva A et al.: A microRNA DNA methylation signature for human cancer metastasis. Proc. Natl Acad. Sci. USA 105(36),13556-13561 (2008). 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.

Up to 90% of cancer deaths are due to metastasis from the primary site. Lymph node metastasis is one of the most common features among almost all solid tumors. The ability to clarify the mechanism underlying metastasis and predict metastasis from analysis of primary disease can have substantial clinical benefit. Recent studies have demonstrated that microRNAs (miRNAs), which are small, noncoding RNAs, play important roles in carcinogenesis with oncogene or tumor suppressor gene activity. In addition, we have learned that some miRNAs are aberrantly methylated and silenced, causing tumorigenesis. In this study, researchers aberrantly methylated and silenced miRNAs that are cancer specific after first identifying candidate miRNAs using 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. This knowledge may be applicable for the advancement of research in the clinical setting.

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