title: MiR-145 directly targets p70S6K1 in cancer cells to inhibit tumor growth and angiogenesis.
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.
authors.affiliation: State Key lab of Reproductive Medicine, and Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Liu
authors.forename: Xu
authors.initials: X
authors.lastname: Qian
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Lihui
authors.initials: L
authors.lastname: Lai
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A; D038762:Ribosomal Protein S6 Kinases, 70-kDa