MicroRNA-105 promotes epithelial-mesenchymal transition of nonsmall lung cancer cells through upregulating Mcl-1 (Retracted article. See vol. 122, 2021)
MicroRNA-105 promotes epithelial-mesenchymal transition of nonsmall lung cancer cells through upregulating Mcl-1 (Retracted article. See vol. 122, 2021)
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DOI：
10.1002/jcb.27873
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发表时间：
2019-04-01
影响因子：
4
通讯作者：
Wang, Zizong
中科院分区：
文献类型：
--
作者：
Jin, Xiangfeng;Yu, Yi;Wang, Zizong
背景越来越多的microRNA被证实在限制肿瘤生长和非小细胞肺癌（NSCLC）的上皮-间质转化（EMT）过程中发挥重要作用。本工作旨在研究microRNA（miR）-105在NSCLC细胞EMT中的作用，但其作用机制尚不清楚。方法将miR-105模拟物、抑制剂和乱序对照分别转染A549和Calu-3两种NSCLC细胞系。通过台盼蓝染色、transwell法、ANNEXIN-FITC/PI双染和Western blot分析，观察miR-105对细胞增殖的影响。用实时定量PCR和Western blot检测转染后骨髓细胞白血病-1（Mcl-1）的表达水平。评估Mcl-1是否是miR-105的下游效应子，以及哺乳动物雷帕霉素靶蛋白（mTOR）和p38丝裂原活化蛋白激酶（p38 MAPK）信号通路的参与。结果miR-105过表达可显著增加A549和Calu-3细胞的存活率和迁移能力，但对细胞凋亡无影响。同时，E-cadherin显著下调，N-cadherin，Vimentin，ZEB 1和Snail通过miR-105过表达上调。Mcl-1受miR-105的正调控，miR-105过表达对A549和Calu-3细胞存活、迁移和EMT的影响均被Mcl-1沉默所抵消。mTOR和p38 MAPK通路在miR-105过表达和Mcl-1过表达的细胞中均被激活。此外，用雷帕霉素和VX-702阻断mTOR和p38 MAPK通路，可使Mcl-1对EMT的调节作用消失。结论miR-105在调节NSCLC细胞EMT中的作用。miR-105可能通过上调Mcl-1从而激活mTOR和p38 MAPK信号通路促进NSCLC细胞的EMT。
Background A growing number of microRNAs have been proved to play significant roles in limiting tumor growth and the epithelial-mesenchymal transition (EMT) process of nonsmall cell lung cancer (NSCLC). Present work aims to study the function of microRNA (miR)-105 in EMT of NSCLC cells, which is unrevealed yet. Methods Two NSCLC cell lines A549 and Calu-3 were transfected with miR-105 mimic, inhibitor, or scrambled control. And then the effects of miR-105 were evaluated by performing trypan blue staining, transwell assay, ANNEXIN-FITC/propidium iodide (PI) double staining and Western blot analysis. The expression levels of myeloid cell leukemia-1 (Mcl-1) after transfection were tested by real-time quantitative polymerase chain reaction and Western blot analysis. Whether Mcl-1 was a downstream effector of miR-105, and the involvement of mammalian target of Rapamycin (mTOR) and p38 mitogen-activated protein kinase (p38MAPK) signaling pathways were assessed. Results The overexpression of miR-105 significantly increased the viability and migration of A549 and Calu-3, but had no impacts on cell apoptosis. Meanwhile, E-cadherin was remarkably downregulated, and N-cadherin, Vimentin, ZEB1, and Snail were upregulated by miR-105 overexpression. Mcl-1 was positively regulated by miR-105, and the effects of miR-105 overexpression on A549 and Calu-3 cells viability, migration and EMT were all flattened by Mcl-1 silence. Both mTOR and p38MAPK pathways were activated in miR-105-overexpressing and Mcl-1-overexpressing cells. Besides, inhibition of mTOR and p38MAPK pathways by using Rapamycin and VX-702 abolished the regulatory effects of Mcl-1 on EMT. Conclusion Our study underlines the importance of miR-105 in modulating NSCLC cells EMT. miR-105 promoted the EMT of NSCLC cells possibly via upregulation of Mcl-1 and thereby activation of mTOR and p38MAPK signaling.