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PMID: 18755897 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

miR-34a repression of SIRT1 regulates apoptosis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 105 ·No. 36 ·2008-09-09 ·Pages 13421-6

Yamakuchi M, Ferlito M, Lowenstein CJ

Abstract

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.

MeSH Terms
Acetylation Apoptosis Base Sequence Cell Line Down-Regulation/genetics Humans MicroRNAs/genetics Sirtuin 1 Sirtuins/genetics,metabolism Tumor Suppressor Protein p53/genetics,metabolism
Chemicals
MicroRNAs Tumor Suppressor Protein p53 SIRT1 protein, human Sirtuin 1 Sirtuins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Yamakuchi Munekazu
Departments of Medicine and Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. myamaku1@jhmi.edu
Ferlito Marcella
Lowenstein Charles J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0801613105
Email
myamaku1@jhmi.edu
Published
2008-09-09
Epub
2008-00-28
Pages
13421-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2533205
Subset
IM
Grants
NHLBI NIH HHS · P01HL65608 · United States
NHLBI NIH HHS · P01 HL065608 · United States
NHLBI NIH HHS · R01 HL078635 · United States
NHLBI NIH HHS · P01 HL056091 · United States
NHLBI NIH HHS · P01HL56091 · United States
NHLBI NIH HHS · R01HL074061 · United States
NHLBI NIH HHS · R01HL78635 · United States
NHLBI NIH HHS · R01 HL074061 · United States
External Links
PubMed source DOI: 10.1073/pnas.0801613105 PMC Full Text View journal details
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