miR-34a repression of SIRT1 regulates apoptosis

Proceedings of the National Academy of Sciences of the United States of America - Tập 105 Số 36 - Trang 13421-13426 - 2008
Munekazu Yamakuchi1, Marcella Ferlito2,3, Charles J. Lowenstein4,5
1Departments of Medicine and Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2Ross Building, 720 Rutland Avenue, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205.
3Yale University, New Haven, CT
4Departments of Medicine, and
5Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

10.1073/pnas.86.10.3753

10.1002/1097-0215(20001201)88:5<772::AID-IJC14>3.0.CO;2-W

10.1016/0165-4608(95)00064-V

JF Moley, et al., Consistent association of 1p loss of heterozygosity with pheochromocytomas from patients with multiple endocrine neoplasia type 2 syndromes. Cancer Res 52, 770–774 (1992).

M Genuardi, H Tsihira, DE Anderson, GF Saunders, Distal deletion of chromosome Ip in ductal carcinoma of the breast. Am J Hum Genet 45, 73–82 (1989).

10.1002/1098-2264(200007)28:3<269::AID-GCC4>3.0.CO;2-K

10.1002/gcc.20408

I Leister, et al., Human colorectal cancer: High frequency of deletions at chromosome 1p35. Cancer Res 50, 7232–7235 (1990).

10.1053/gast.1996.v111.pm8698188

10.1002/(SICI)1098-2264(199803)21:3<185::AID-GCC2>3.0.CO;2-W

10.1038/sj.neo.7900111

10.1007/s10585-005-5239-7

K Tanaka, et al., Suppression of tumourigenicity in human colon carcinoma cells by introduction of normal chromosome 1p36 region. Oncogene 8, 2253–2258 (1993).

10.1038/sj.onc.1210293

10.1016/j.molcel.2007.05.010

10.1016/S0092-8674(04)00045-5

10.1038/nature02873

10.1126/science.1111444

10.1038/nature02871

10.1016/j.molcel.2004.12.002

10.1016/0092-8674(93)90529-Y

10.1016/S0960-9822(03)00250-1

10.1016/0092-8674(93)90530-4

10.1038/35002607

10.1016/S0092-8674(03)00231-9

10.1038/nature03816

MZ Michael, et al., Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 1, 882–891 (2003).

10.1073/pnas.0307323101

10.1158/0008-5472.CAN-05-1783

10.1038/nature03702

10.1038/nature03552

10.1073/pnas.0510565103

10.1158/0008-5472.CAN-06-3613

10.2217/14796694.2.1.73

10.1073/pnas.0506654102

10.1016/j.cell.2005.01.014

10.1158/0008-5472.CAN-04-0637

10.1126/science.1137999

JP Morris, MT McManus, Slowing down the Ras lane: miRNAs as tumor suppressors? Sci STKE 41 (2005).

10.1038/nrc2232

10.1073/pnas.0707351104

10.1038/nature05939

10.4161/cc.6.13.4436

10.1016/j.molcel.2007.05.017

10.1101/gad.1467506

10.1016/j.cell.2006.07.002

10.1073/pnas.0409875102

10.1158/0008-5472.CAN-07-0085

10.1007/s00403-006-0725-6

10.1038/sj.emboj.7600244

10.1016/S0092-8674(01)00524-4

10.1016/S0092-8674(01)00527-X

10.1093/emboj/21.10.2383

10.1073/pnas.1934713100

10.1038/35042675

10.1038/nm1087

10.1038/35042612

10.1016/j.cell.2005.08.011

10.1158/0008-5472.CAN-05-3617

10.1038/sj.onc.1209049

Thông tin
Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 105 Số 36

13421-13426

Thông tin tác giả