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  • 标题:miR-34a repression of SIRT1 regulates apoptosis
  • 本地全文:下载
  • 作者:Munekazu Yamakuchi ; Marcella Ferlito ; Charles J. Lowenstein
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2008
  • 卷号:105
  • 期号:36
  • 页码:13421-13426
  • DOI:10.1073/pnas.0801613105
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:MicroRNA 34a (miR-34a) is a tumor suppressor gene, but how it regulates cell proliferation is not completely understood. We now show that the microRNA miR-34a regulates silent information regulator 1 (SIRT1) expression. MiR-34a inhibits SIRT1 expression through a miR-34a-binding site within the 3' UTR of SIRT1. MiR-34 inhibition of SIRT1 leads to an increase in acetylated p53 and expression of p21 and PUMA, transcriptional targets of p53 that regulate the cell cycle and apoptosis, respectively. Furthermore, miR-34 suppression of SIRT1 ultimately leads to apoptosis in WT human colon cancer cells but not in human colon cancer cells lacking p53. Finally, miR-34a itself is a transcriptional target of p53, suggesting a positive feedback loop between p53 and miR-34a. Thus, miR-34a functions as a tumor suppressor, in part, through a SIRT1-p53 pathway.
  • 关键词:microRNA ; p53 ; cancer
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