Li Gang, Wang Kai, Wang Jiansheng, Qin Sida, Sun Xin, Ren Hong
The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Department of Oncology, Traditional Chinese Medicine Hospital of Shaanxi Province, Xi'an, People's Republic of China.
J Cell Biochem. 2019 Jun;120(6):10587-10595. doi: 10.1002/jcb.28345. Epub 2019 Feb 28.
MicroRNAs plays an important role in the ccurrence and development of non-small-cell lung cancer (NSCLC). miR-497-5p has been reported to function as a tumor suppressor in various cancers. However, the role of miR-497-5p in NSCLC remains poorly understood. In this study, we aimed to investigate the biological role and potential molecular mechanism of miR-497-5p in NSCLC. Our results showed that the messenger RNA (mRNA) expression level of miR-497-5p was notably downregulated in human NSCLC tissues and cell lines. miR-497-5p overexpression remarkably inhibited NSCLC cell proliferation and increased cell apoptosis in A549 and H460 cells, whereas inhibition of miR-497-5p had an opposite effect. The ability of cell migration and invasion was inhibited by miR-497-5p overexpression but was increased by miR-497-5p inhibition. Moreover, our findings indicated that SOX5 was a direct target of miR-497-5p. The protein and mRNA expression levels of SOX5 in A549 cells were remarkably inhibited by miR-497-5p overexpression but was upregulated by miR-497-5p inhibition. Furthermore, SOX5 overexpression notably reversed the effect of miR-497-5p mimic on NSCLC cell proliferation, cell apoptosis, cell migration, and invasion. Taken together, these results indicated that miR-497-5p overexpression inhibited NSCLC cell proliferation, migration and invasion, and induced cell apoptosis through inhibiting SOX5 gene expression. It was conceivable that miR-497-5p might serve as a potential molecular target for NSCLC treatment.
微小RNA在非小细胞肺癌（NSCLC）的发生和发展中起重要作用。据报道，miR-497-5p在多种癌症中发挥肿瘤抑制作用。然而，miR-497-5p在NSCLC中的作用仍知之甚少。在本研究中，我们旨在探讨miR-497-5p在NSCLC中的生物学作用及潜在分子机制。我们的结果表明，miR-497-5p的信使核糖核酸（mRNA）表达水平在人NSCLC组织和细胞系中显著下调。miR-497-5p过表达显著抑制A549和H460细胞中的NSCLC细胞增殖并增加细胞凋亡，而抑制miR-497-5p则产生相反的效果。miR-497-5p过表达抑制细胞迁移和侵袭能力，但miR-497-5p抑制则增强该能力。此外，我们的研究结果表明SOX5是miR-497-5p的直接靶标。miR-497-5p过表达显著抑制A549细胞中SOX5的蛋白质和mRNA表达水平，但miR-497-5p抑制则使其上调。此外，SOX5过表达显著逆转了miR-497-5p模拟物对NSCLC细胞增殖、细胞凋亡、细胞迁移和侵袭的影响。综上所述，这些结果表明miR-497-5p过表达通过抑制SOX5基因表达来抑制NSCLC细胞增殖、迁移和侵袭，并诱导细胞凋亡。可以想象，miR-497-5p可能成为NSCLC治疗的潜在分子靶点。
