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miR-149 通过抑制 FOXM1/细胞周期蛋白 D1/MMP2 轴抑制人非小细胞肺癌的生长和转移。

miR-149 suppresses human non-small cell lung cancer growth and metastasis by inhibiting the FOXM1/cyclin D1/MMP2 axis.

机构信息

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.

出版信息

Oncol Rep. 2017 Dec;38(6):3522-3530. doi: 10.3892/or.2017.6047. Epub 2017 Oct 20.

Abstract

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.

摘要

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。

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