TY - JOUR
T1 - miR-34a repression of SIRT1 regulates apoptosis
AU - Yamakuchi, Munekazu
AU - Ferlito, Marcella
AU - Lowenstein, Charles J.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/9/9
Y1 - 2008/9/9
N2 - 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.
AB - 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.
KW - Cancer
KW - microRNA
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=51649115553&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=51649115553&partnerID=8YFLogxK
U2 - 10.1073/pnas.0801613105
DO - 10.1073/pnas.0801613105
M3 - Article
C2 - 18755897
AN - SCOPUS:51649115553
VL - 105
SP - 13421
EP - 13426
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 36
ER -