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Nucleic Acids Res. 2012 Jan;40(2):761-74. doi: 10.1093/nar/gkr730. Epub 2011 Sep 14.

MiR-145 directly targets p70S6K1 in cancer cells to inhibit tumor growth and angiogenesis.

Author information

1
State Key lab of Reproductive Medicine, and Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing, China.

Abstract

MiR-145 can regulate cell apoptosis, proliferation, neural development and stem cell differentiation. Previous studies indicate that miR-145 is downregulated in human colon cancer cells. However, the molecular mechanisms of miR-145 used to regulate colon carcinogenesis and angiogenesis remain to be clarified. Here, we show that the expression of miR-145 is downregulated in colon and ovarian cancer tissues and cell lines. MiR-145 inhibits p70S6K1 post-transcriptional expression by binding to its 3'-UTR. The angiogenic factors hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF), which are downstream molecules of p70S6K1, are decreased by miR-145 overexpression. P70S6K1 rescues miR-145-suppressed HIF-1 and VEGF levels, tumorigenesis and tumor angiogenesis. Furthermore, the miR-145 level is inversely correlated with the amount of p70S6K1 protein in colon cancer tissues. Taken together, these studies suggest that miR-145 serves as a tumor suppressor which downregulates HIF-1 and VEGF expression by targeting p70S6K1, leading to the inhibition of tumor growth and angiogenesis. The miR-145 rescue could be a rationale for therapeutic applications in colon cancer in the future.

PMID:
21917858
PMCID:
PMC3258133
DOI:
10.1093/nar/gkr730
[Indexed for MEDLINE]
Free PMC Article

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