Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
PLoS One. 2013 Sep 10;8(9):e73604. doi: 10.1371/journal.pone.0073604. eCollection 2013.
MicroRNAs (miRNAs) are a class of small noncoding RNA molecules that play important roles in carcinogenesis and tumor progression. In this study, we investigated the roles and mechanisms of miR-140 in human non-small cell lung cancer (NSCLC). We found that miR-140 is significantly downregulated in NSCLC tissues and cell lines. Both gain-of-function and loss-of-function studies demonstrated that miR-140 suppresses NSCLC cell proliferation, migration, and invasion in vitro. Importantly, overexpression of miR-140 effectively repressed tumor growth and metastasis in nude mouse models. Integrated analysis identified IGF1R as a direct and functional target of miR-140. Knockdown of IGF1R inhibited cell proliferation and invasion resembling that of miR-140 overexpression, while overexpression of IGF1R attenuated the function of miR-140 in NSCLC cells. Together, our results highlight the significance of miR-140 and IGF1R in the development and progression of NSCLC.
微小 RNA(miRNAs)是一类小的非编码 RNA 分子,在癌症发生和肿瘤进展中发挥重要作用。在这项研究中,我们研究了 miR-140 在人非小细胞肺癌(NSCLC)中的作用和机制。我们发现 miR-140 在 NSCLC 组织和细胞系中显著下调。功能获得和功能丧失研究均表明,miR-140 可抑制 NSCLC 细胞在体外的增殖、迁移和侵袭。重要的是,miR-140 的过表达可有效抑制裸鼠模型中的肿瘤生长和转移。整合分析确定 IGF1R 是 miR-140 的直接和功能靶标。IGF1R 的敲低抑制细胞增殖和侵袭,类似于 miR-140 的过表达,而过表达 IGF1R 则减弱了 miR-140 在 NSCLC 细胞中的功能。总之,我们的研究结果突出了 miR-140 和 IGF1R 在 NSCLC 发生和进展中的重要性。