MicroRNA-301 a promotes growth and migration by repressing TGFBR 2 in non-small cell lung cancer

MicroRNA-301 a promotes growth and migration by repressing TGFBR 2 in non-small cell lung cancer
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发表时间:
2017
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通讯作者:
Quanmei Chen;Yun Li;Chunxue Zhang;Yitao Wang;Lian Zhang;Fangzhou Song;You-quan;Bu
Quanmei Chen;Yun Li;Chunxue Zhang;Yitao Wang;Lian Zhang;Fangzhou Song;You-quan;Bu
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其他
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作者:
Quanmei Chen;Yun Li;Chunxue Zhang;Yitao Wang;Lian Zhang;Fangzhou Song;You-quan;Bu

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最近的一些研究报告miR-301a显著上调,并与几种类型的人类癌症有关。然而,miR-301a在非小细胞肺癌(NSCLC)中的功能参与在很大程度上仍不清楚。在此,我们分别使用miR-301a模拟物和抑制剂来调控NSCLC细胞中miR-301a的表达。我们的研究结果表明,miR-301a在非小细胞肺癌组织中的表达显著高于正常肺组织。MiR-301a过表达显著促进肺癌细胞的增殖和迁移。相反,抑制miR-301a显著抑制细胞的生长和运动。系统靶基因分析表明,TGFBR2是肺癌细胞中受miR-301a负调控的关键下游靶基因。值得注意的是,TGFBR2在非小细胞肺癌组织中的表达显著下调,并与miR-301的表达呈负相关。在非小细胞肺癌组织中,转化生长因子-β信号基因的表达水平一直受miR-301a的调控,并且与miR-301a的表达水平呈负相关。此外,在非小细胞肺癌患者中,TGFBR2的低表达与较差的生存显著相关。研究表明,miR-301a通过靶向TGFBR2调控转化生长因子-β信号通路,促进肺癌细胞的生长和迁移。
A number of recent studies reported that miR-301a was significantly up-regulated and implicated in several types of human cancers. However, the functional involvement of miR-301a in non-small cell lung cancer (NSCLC) remains largely unknown. Herein, miR-301a mimics and inhibitors were used to manipulate miR-301a expression in NSCLC cells, respectively. Our findings revealed that miR-301a expression was significantly up-regulated in nonsmall cell lung cancer (NSCLC) tissues compared with normal lung tissues. Overexpression of miR-301a significantly enhanced proliferation and migration in lung cancer cells. Conversely, inhibition of miR-301a remarkably suppressed cell growth and motility. Systemic target gene analysis demonstrated that TGFBR2 is a critical downstream target negatively regulated by miR-301a in lung cancer cells. Notably, TGFBR2 expression was remarkably downregulated and inversely correlated with miR-301 expression in NSCLC tissues. Consistently, the expression levels of TGF-β signaling genes were modulated by miR-301a, and negatively correlated with that of miR-301a in NSCLC tissues. Moreover, low TGFBR2 expression was significantly associated with poorer survival in NSCLC patients. Out data indicated that miR-301a promotes cell growth and migration by targeting TGFBR2 to modulate TGF-β signaling pathway in lung cancer.