Department of Respiratory, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China.
Department of Laboratory, People's Hospital of Rizhao, Rizhao, Shandong 276826, P.R. China.
Oncol Rep. 2017 Dec;38(6):3522-3530. doi: 10.3892/or.2017.6047. Epub 2017 Oct 20.
Valid evidence has demonstrated that microRNAs have critical functions in cancer genesis and tumor progression. In the present study, aberrant expression of microRNA-149 (miR-149) was confirmed in non-small cell lung cancer (NSCLC) tissues. Low expression of miR-149 was associated with malignant clinical features and poor survival. Gain- and loss-of-function experiments demonstrated that miR-149 inhibited NSCLC tumor growth and metastasis in vitro and in vivo. Furthermore, oncogenic transcription factor FOXM1 was confirmed as a direct target of miR-149 in NSCLC. Cyclin D1 and MMP2 served as downstream targets of FOXM1 and were also inhibited by miR-149. In summary, the present study indicated that downregulation of miR-149 in NSCLC predicted poor clinical outcomes. miR-149 suppresses tumor growth and metastasis in NSCLC by inhibiting the FOXM1/cyclin D1/MMP2 signaling pathway.
已有充分证据表明，microRNAs 在癌症发生和肿瘤进展中具有关键作用。本研究证实，microRNA-149（miR-149）在非小细胞肺癌（NSCLC）组织中存在异常表达。miR-149 的低表达与恶性临床特征和不良生存相关。增益和缺失功能实验表明，miR-149 可抑制 NSCLC 的体外和体内肿瘤生长和转移。此外，致癌转录因子 FOXM1 被确认为 NSCLC 中 miR-149 的直接靶标。细胞周期蛋白 D1 和 MMP2 是 FOXM1 的下游靶标，也受到 miR-149 的抑制。综上所述，本研究表明 NSCLC 中 miR-149 的下调预示着不良的临床结局。miR-149 通过抑制 FOXM1/细胞周期蛋白 D1/MMP2 信号通路抑制 NSCLC 中的肿瘤生长和转移。
