Authors: Likun Hou Jian Chen Yuhui Zheng Chunyan Wu
Publish Date: 2015/11/09
Volume: 37, Issue: 4, Pages: 5185-5192
Abstract
Lung cancer is the leading cause of cancerrelated deaths in the world and nonsmall cell lung carcinomas NSCLC account for 85 of lung cancer cases Despite enormous achievement in the treatment of NSCLC the molecular mechanisms underlying the pathogenesis are largely unknown The current study was designed to evaluate the role of miR155 in NSCLC cell proliferation and to explore the possible molecular mechanisms We found that miR155 expression was increased in NSCLC tissues and cell lines The increase of miR155 significantly increased A549 cell proliferation decreased S phase cell population and increased G2/M phase cell population Decrease of miR155 expression markedly inhibited cell proliferation increased S phase cell population and decreased G2/M phase cell population Increase of miR155 significantly decreased forkhead box protein O1 FoxO1 3’UTR luciferase activity and expression and decrease of miR155 notably increased FoxO1 expression Overexpression of FoxO1 significantly inhibited miR155exerted increase of cell proliferation and G2/M cell population Downregulation of FoxO1 by siRNAs significantly promoted cell proliferation decreased S phase cell numbers and increased G2/M cell population Downregulation of FoxO1 markedly increased ROS level as reflected by increased DHE staining Moreover when Nacetylcysteine was present increase of cell proliferation induced by downregulation of FoxO1 and upregulation of miR155 was significantly inhibited In conclusion we found that miR155 promoted NSCLC cell proliferation through inhibition of FoxO1 and the subsequent increase of ROS generation Our findings highlight miR155/FoxO1/ROS axis as a novel therapeutic target for the inhibition of NSCLC growth
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