Comprehensive silencing of target-sharing micrornas is a mechanism for SIRT1 overexpression in cancer

Kotaro Kiga, Yoko Fukuda-Yuzawa, Masanobu Tanabe, Shoji Tsuji, Chihiro Sasakawa, Taro Fukao

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Overexpression of SIRT1 is frequently observed in various types of cancers, suggesting its potential role in malignancies. However, the molecular basis of how SIRT1 is elevated in cancer is less understood. Here we show that cancer-related SIRT1 overexpression is due to evasion of Sirt1 mRNA from repression by a group of Sirt1-targeting microRNAs (miRNAs) that might be robustly silenced in cancer. Our comprehensive library-based screening and subsequent miRNA gene profiling revealed a housekeeping gene-like broad expression pattern and strong CpG islandassociation of the Sirt1-targeting miRNA genes. This suggests aberrant CpG DNA methylation as the mechanistic background for malignant SIRT1 elevation. Our work also provides an example where epigenetic mechanisms cause the group-wide regulation of miRNAs sharing a common key target.

Original languageEnglish
Pages (from-to)1347-1354
Number of pages8
JournalRNA Biology
Volume11
Issue number11
DOIs
Publication statusPublished - 2014 Nov 1

Keywords

  • Cancer
  • DNA methylation
  • Epigenetics
  • MicroRNA
  • SIRT1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Comprehensive silencing of target-sharing micrornas is a mechanism for SIRT1 overexpression in cancer'. Together they form a unique fingerprint.

Cite this