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

研究成果: Article査読

11 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1347-1354
ページ数8
ジャーナルRNA Biology
11
11
DOI
出版ステータスPublished - 2014 11 1

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学

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