Zhang Zuxiong, Li Weizhi, Jiang Damei, Liu Chi, Lai Zhenghong
Department of Cardiothoracic Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.
Department of Radiotherapy, Tumor Hospital of Ganzhou, Ganzhou, Jiangxi 341000, P.R. China.
Oncol Lett. 2020 Mar;19(3):1806-1814. doi: 10.3892/ol.2020.11296. Epub 2020 Jan 13.
MicroRNA (miRNAs) serve key roles in the progress of various types of cancer. The expression of miRNA (miR)-139-5p is downregulated in several types of tumor and has been recognized as a tumor suppressor. However, the role of miR-139-5p in non-small cell lung cancer (NSCLC) has not been investigated in detail. In the present study, it was demonstrated that miR-139-5p was significantly downregulated in NSCLC cells and tissues, and the overexpression of miR-139-5p induced apoptosis and significantly inhibited the viability and proliferation of A549 and H1299 cells. In addition, upregulation of miR-139-5p significantly inhibited the migration and invasion of A549 and H1299 cells. Hepatoma-derived growth factor (HDGF) was identified as a direct target of miR-139-5p. Rescue experiments demonstrated that the inhibitory function of miR-139-5p on cell viability, migration and invasion was partially mediated by suppressing HDGF expression. Furthermore, miR-139-5p exhibited efficient inhibition of tumor growth in a xenograft tumor mouse model of A549 cells. In summary, the results from the present study suggested that miR-139-5p may serve an important role in NSCLC by targeting HDGF and causing inhibition of cell viability and metastasis, as well as induction of apoptosis. miR-139-5p may also have the potential to serve as a therapeutic target for the treatment of NSCLC.
微小RNA(miRNA)在各类癌症进展中发挥关键作用。miRNA(miR)-139-5p在多种肿瘤类型中表达下调,并已被确认为一种肿瘤抑制因子。然而,miR-139-5p在非小细胞肺癌(NSCLC)中的作用尚未得到详细研究。在本研究中,结果表明miR-139-5p在NSCLC细胞和组织中显著下调,miR-139-5p的过表达诱导细胞凋亡,并显著抑制A549和H1299细胞的活力和增殖。此外,miR-139-5p的上调显著抑制A549和H1299细胞的迁移和侵袭。肝癌衍生生长因子(HDGF)被鉴定为miR-139-5p的直接靶标。挽救实验表明,miR-139-5p对细胞活力、迁移和侵袭的抑制作用部分是通过抑制HDGF表达介导的。此外,在A549细胞的异种移植肿瘤小鼠模型中,miR-139-5p对肿瘤生长表现出有效的抑制作用。总之,本研究结果表明,miR-139-5p可能通过靶向HDGF并抑制细胞活力和转移以及诱导细胞凋亡,在NSCLC中发挥重要作用。miR-139-5p也有可能成为NSCLC治疗的一个治疗靶点。