A microRNA component of the p53 tumour suppressor network.
A global decrease in microRNA (miRNA) levels is often observed in human cancers, indicating that small RNAs may have an intrinsic function in tumour suppression. To identify miRNA components of tumour suppressor pathways, we compared miRNA expression profiles of wild-type and p53-deficient cells. Here we describe a family of miRNAs, miR-34a-c, whose expression reflected p53 status. Genes encoding miRNAs in the miR-34 family are direct transcriptional targets of p53, whose induction by DNA damage and oncogenic stress depends on p53 both in vitro and in vivo. Ectopic expression of miR-34 induces cell cycle arrest in both primary and tumour-derived cell lines, which is consistent with the observed ability of miR-34 to downregulate a programme of genes promoting cell cycle progression. The p53 network suppresses tumour formation through the coordinated activation of multiple transcriptional targets, and miR-34 may act in concert with other effectors to inhibit inappropriate cell proliferation.
He
Lin
L
Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
He
Xingyue
X
Lim
Lee P
LP
de Stanchina
Elisa
E
Xuan
Zhenyu
Z
Liang
Yu
Y
Xue
Wen
W
Zender
Lars
L
Magnus
Jill
J
Ridzon
Dana
D
Jackson
Aimee L
AL
Linsley
Peter S
PS
Chen
Caifu
C
Lowe
Scott W
SW
Cleary
Michele A
MA
Hannon
Gregory J
GJ
D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D004249:DNA Damage; D005786:Gene Expression Regulation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D013379:Substrate Specificity; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53