MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression.
Ling-Zhi Liu,Chongyong Li,Qi Chen,Yi Jing,Richard L. Carpenter,Yue Jiang,Hsiang-Fu Kung,Lihui Lai,Bing-Hua Jiang,Bing-Hua Jiang +9 more
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TLDR
It is demonstrated that miR-21 induces tumor angiogenesis through targeting PTEN, leading to activate AKT and ERK1/2 signaling pathways, and thereby enhancing Hif-1α and VEGF expression; HIF-1 α is a key downstream target of miR -21 in regulating tumorAngiogenesis.Abstract:
MicroRNAs (miRNAs) are endogenous, small noncoding RNAs that play important roles in various cellular functions and tumor development. Recent studies have indicated that miR-21 is one of the important miRNAs associated with tumor growth and metastasis, but the role and molecular mechanism of miR-21 in regulating tumor angiogenesis remain to be elucidated. In this study, miR-21 was overexpressed by transfecting pre-miR-21 into human prostate cancer cells and tumor angiogenesis was assayed using chicken chorioallantoic membrane (CAM). We found that overexpression of miR-21 in DU145 cells increased the expression of HIF-1α and VEGF, and induced tumor angiogenesis. AKT and extracellular regulated kinases (ERK) 1/2 are activated by miR-21. Inhibition of miR-21 by the antigomir blocked this process. Overexpression of the miR-21 target, PTEN, also inhibited tumor angiogenesis by partially inactivating AKT and ERK and decreasing the expression of HIF-1 and VEGF. The AKT and ERK inhibitors, LY294002 and U0126, suppressed HIF-1α and VEGF expression and angiogenesis. Moreover, inhibition of HIF-1α expression alone abolished miR-21-inducing tumor angiogenesis, indicating that HIF-1α is required for miR-21-upregulated angiogenesis. Therefore, we demonstrate that miR-21 induces tumor angiogenesis through targeting PTEN, leading to activate AKT and ERK1/2 signaling pathways, and thereby enhancing HIF-1α and VEGF expression; HIF-1α is a key downstream target of miR-21 in regulating tumor angiogenesis.read more
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The role of MicroRNAs in human cancer
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Regulation of Hypoxia‐Inducible Factor‐1a by Reactive Oxygen Species : New Developments in an Old Debate
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MicroRNAs in Human Placental Development and Pregnancy Complications
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References
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