Pan Yi, Ye Conglin, Tian Qingshan, Yan Songxin, Zeng Xiaoping, Xiao Chu, Wang Lingyun, Wang Hongmei
School of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Department of Orthopedics, Artificial Joints Engineering and Technology Research Center of Jiangxi Province, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Oncol Lett. 2018 Apr;15(4):4337-4343. doi: 10.3892/ol.2018.7863. Epub 2018 Jan 25.
Although microRNA (miR)-145 has been identified to be a tumor suppressor in various types of tumor, it promotes the progression of non-small cell lung cancer (NSCLC). However, the precise underlying molecular mechanism of its action remains unclear. The present study investigated the effects of miR-145 on the proliferation, invasion, metastasis and apoptosis of the NSCLC A549 cell line and the underlying molecular mechanism of its action. cell proliferation, invasion, migration and apoptosis assays were employed, and the expression levels of matrix metalloproteinase (MMP)-2, MMP-9, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3and poly(ADP-ribose) polymerase (PARP) were evaluated by western blot analysis. The results demonstrated that ectopic expression of miR-145 inhibited the proliferation, invasion and migration of A549 cells, but promoted the apoptosis of A549 cells. Western blot analysis indicated that increased miR-145 levels led to a marked decrease in the expression of MMP-2, MMP-9 and Bcl-2. Upregulation of miR-145 expression increased the expression of Bax, thus increasing the Bax/Bcl-2 ratio. Additionally, the results indicated that miR-145 over expression promoted the cleavage of caspase-3 and PARP. Taken together, these results indicated that miR-145 suppresses the proliferative, invasive and migratory ability of A549 cells. Additionally, miR-145 upregulation induced apoptosis of A549 cells possibly by decreasing MMP-2 and MMP-9 expression, the Bax/Bcl-2 ratio and the activity of the caspase-3 cascade.
尽管微小RNA(miR)-145已被确定为多种肿瘤中的肿瘤抑制因子,但它却促进非小细胞肺癌(NSCLC)的进展。然而,其作用的确切潜在分子机制仍不清楚。本研究调查了miR-145对NSCLC A549细胞系增殖、侵袭、转移和凋亡的影响及其作用的潜在分子机制。采用细胞增殖、侵袭、迁移和凋亡检测,并通过蛋白质印迹分析评估基质金属蛋白酶(MMP)-2、MMP-9、B细胞淋巴瘤2(Bcl-2)、Bcl-2相关X蛋白(Bax)、半胱天冬酶-3和聚(ADP-核糖)聚合酶(PARP)的表达水平。结果表明,miR-145的异位表达抑制了A549细胞的增殖、侵袭和迁移,但促进了A549细胞的凋亡。蛋白质印迹分析表明,miR-145水平升高导致MMP-2、MMP-9和Bcl-2的表达显著降低。miR-145表达上调增加了Bax的表达,从而增加了Bax/Bcl-2比值。此外结果表明,miR-145过表达促进了半胱天冬酶-3和PARP的裂解。综上所述,这些结果表明miR-145抑制A549细胞的增殖、侵袭和迁移能力。此外,miR-145上调可能通过降低MMP-2和MMP-9表达、Bax/Bcl-2比值以及半胱天冬酶-3级联反应的活性诱导A549细胞凋亡。