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Roles and mechanism of miR-199a and miR-125b in tumor angiogenesis.

ABSTRACT: MicroRNAs (miRNAs) have been shown to be involved in different aspects of cancer biology including tumor angiogenesis. In this study, we identified that two miRNAs, miR-199a and miR-125b were downregulated in ovarian cancer tissues and cell lines. Overexpression of miR-199a and miR-125b inhibited tumor-induced angiogenesis associated with the decrease of HIF-1? and VEGF expression in ovarian cancer cells. Moreover, the levels of miR-199a and miR-125b were negatively correlated with VEGF mRNA levels in ovarian tissues. We further showed that direct targets of miR-199a and miR-125b HER2 and HER3 were functionally relevant. Forced expression of HER2 and HER3 rescued miR-199a- and miR-125b-inhibiting angiogenesis responses and Akt/p70S6K1/HIF-1? pathway. This study provides a rationale for new therapeutic approach to suppress tumor angiogenesis using miR-199a, miR-125b, or their mimics for ovarian cancer treatment in the future.

SUBMITTER: He J

PROVIDER: S-EPMC3577861 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Roles and mechanism of miR-199a and miR-125b in tumor angiogenesis.

He Jun J Jing Yi Y Li Wei W Qian Xu X Xu Qing Q Li Feng-Shan FS Liu Ling-Zhi LZ Jiang Bing-Hua BH Jiang Yue Y

PloS one 20130220 2

MicroRNAs (miRNAs) have been shown to be involved in different aspects of cancer biology including tumor angiogenesis. In this study, we identified that two miRNAs, miR-199a and miR-125b were downregulated in ovarian cancer tissues and cell lines. Overexpression of miR-199a and miR-125b inhibited tumor-induced angiogenesis associated with the decrease of HIF-1α and VEGF expression in ovarian cancer cells. Moreover, the levels of miR-199a and miR-125b were negatively correlated with VEGF mRNA lev ...[more]

PMID: 23437196

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