title: Suppression of AKT expression by miR-153 produced anti-tumor activity in lung cancer.
abstract: Lung cancer is one of the leading causes of cancer death worldwide. microRNAs have been shown to be a novel class of regulators in lung cancer. Here, we explored the role of miR-153 in the pathogenesis of lung cancer and its therapeutic potential. miR-153 was significantly decreased in lung cancer tissues than the adjacent tissues. The protein and mRNA levels of protein kinase B (AKT), which were shown to promote tumor growth, were both increased in lung cancer tissues than adjacent tissues. Overexpression of miR-153 significantly inhibited AKT protein expression, which were abrogated by co-transfection of AMO-153, the specific inhibitor of miR-153. Luciferase assay showed that transfection of miR-153 markedly suppressed the fluorescent intensity of chimeric vectors carrying the 3'UTR of AKT1, while produced no effect on the mutant construct, indicating that AKT is regulated by miR-153. Overexpression of miR-153 significantly inhibited the proliferation and migration, and promoted apoptosis of cultured lung cancer cells in vitro, and suppressed the growth of xenograft tumors in vivo. Interestingly, lung cancer cells with lower endogenous miR-153 expression are more sensitive to ectopic overexpressed miR-153. The IC50 of miR-153 on lung cancer cells is positive correlated with the endogenous miR-153 level, while negative correlated with AKT level. Knockdown of AKT expression suppressed lung cancer cell proliferation. In summary, miR-153 exerted anti-tumor activity in lung cancer by targeting on AKT. The sensitivity of lung cancer cells to miR-153 is determined by its endogenous miR-153 level.
authors: Department of Pharmacology, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
authors: Ye
authors: Y
authors: Yuan
authors: Weijie
authors: W
authors: Du
authors: Ying
authors: Y
authors: Wang
authors: Chaoqian
authors: C
authors: Xu
authors: Jinghao
authors: J
authors: Wang
authors: Yang
authors: Y
authors: Zhang
authors: Huimin
authors: H
authors: Wang
authors: Jiaming
authors: J
authors: Ju
authors: Liang
authors: L
authors: Zhao
authors: Zhiguo
authors: Z
authors: Wang
authors: Yanjie
authors: Y
authors: Lu
authors: Benzhi
authors: B
authors: Cai
authors: Zhenwei
authors: Z
authors: Pan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
chemical_list: C556500:MIRN153 microRNA, human; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; lung cancer; miR-153; proliferation