MicroRNA-141 promotes the proliferation of non-small cell lung cancer cells by regulating expression of PHLPP1 and PHLPP2

MicroRNA-141 promotes the proliferation of non-small cell lung cancer cells by regulating expression of PHLPP1 and PHLPP2
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MicroRNA-141通过调节PHLPP1和PHLPP2表达促进非小细胞肺癌细胞增殖

DOI:
10.1016/j.febslet.2014.06.020
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发表时间:
2014-08-25
期刊:
影响因子:
3.5
通讯作者:
Jie, Zhijun
Jie, Zhijun
中科院分区:
生物学3区
文献类型:
--
作者:
Mei, Zhoufang;He, Yanchao;Jie, Zhijun

文献摘要

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microRNA(miRNAs)的失调与各种癌症的发展密切相关。在这项研究中,我们探讨了miR-141在非小细胞肺癌(NSCLC)中的生物学作用。miR-141在NSCLC组织中表达显著上调,其过表达促进了NSCLC细胞的体外增殖和体内肿瘤的生长。我们随后确定了PI 3 K/AKT信号传导的拮抗剂,PH结构域富含亮氨酸重复序列的蛋白磷酸酶1(PHLPP 1)和PHLPP 2,作为miR-141的直接靶点。PHLPP 1和PHLPP 2的重新引入消除了miR-141诱导的NSCLC细胞增殖。总之,这项研究的结果表明,miR-141及其靶点PHLPP 1和PHLPP 2在NSCLC肿瘤发生中起着关键作用,并为NSCLC治疗提供了潜在的治疗靶点。(C)2014年欧洲生物化学学会联合会。Elsevier B. V.出版,保留所有权利。
The dysregulation of microRNAs (miRNAs) is crucially implicated in the development of various cancers. In this study, we explored the biological role of miR-141 in non-small cell lung cancer (NSCLC). miR-141 expression was significantly up-regulated in NSCLC tissues, and its overexpression accelerated NSCLC cell proliferation in vitro and tumor growth in vivo. We subsequently identified the antagonists of PI3K/AKT signaling, PH domain leucine-rich-repeats protein phosphatase 1 (PHLPP1) and PHLPP2, as direct targets of miR-141. Re-introduction of PHLPP1 and PHLPP2 abrogated miR-141-induced proliferation of NSCLC cells. Together, the results of this study suggest that miR-141 and its targets PHLPP1 and PHLPP2 play critical roles in NSCLC tumorigenesis, and provide potential therapeutic targets for NSCLC treatment. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.