Zheng Hong, Wu Jianbo, Shi Jiachen, Lu Chunya, Wang Yuanyuan, Sun Qianqian, Zhang Guojun, Zhao Guoqiang
Department of Pathophysiology, Institute of Molecular Medicine, Medical College of Henan University, Kaifeng, Henan 475004, P.R. China.
School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
Oncol Rep. 2017 Sep;38(3):1790-1796. doi: 10.3892/or.2017.5812. Epub 2017 Jul 13.
MicroRNAs (miRNAs) are critical translational regulators that act as oncogenes or tumor-suppressor genes. qRT-PCR assay results showed that the expression levels of miR-125a-5p are lower in lung adenocarcinoma (AD) tissues than expression levels in adjacent non-neoplastic tissues. This relative expression was found to be significantly associated with lymph node metastases. Cell growth, apoptosis, caspase activity and Transwell invasion assay results showed that in two lung adenocarcinoma cell lines transfected with a miR-125a-5p mimic, proliferation and invasion rates were found to be significantly reduced, whereas the apoptosis rate of the miR-125a-5p mimic group was enhanced. Subsequent western blotting and luciferase reporter assays showed that miR-125a-5p is able to bind to putative binding sites within the mRNA 3' untranslated region (UTR) of neural precursor cell expressed, developmentally downregulated 9 (NEDD9). Our findings suggest that miR-125a-5p may serve as a therapeutic agent for lung adenocarcinoma through its major target, NEDD9.
微小RNA(miRNA)是作为癌基因或肿瘤抑制基因发挥作用的关键翻译调节因子。定量逆转录聚合酶链反应(qRT-PCR)检测结果显示,肺腺癌(AD)组织中miR-125a-5p的表达水平低于相邻非肿瘤组织中的表达水平。发现这种相对表达与淋巴结转移显著相关。细胞生长、凋亡、半胱天冬酶活性及Transwell侵袭实验结果显示,在转染了miR-125a-5p模拟物的两种肺腺癌细胞系中,增殖和侵袭率显著降低,而miR-125a-5p模拟物组的凋亡率则升高。随后的蛋白质印迹法和荧光素酶报告基因检测表明,miR-125a-5p能够与神经前体细胞表达、发育下调9(NEDD9)的mRNA 3'非翻译区(UTR)内的假定结合位点结合。我们的研究结果表明,miR-125a-5p可能通过其主要靶点NEDD9作为肺腺癌的一种治疗药物。