Han Fei, Chen Gang, Guo Yi, Li Bo, Sun Yanlong, Qi Xiangqian, Tian Hanji, Zhao Xinfei, Zhang Hongguang
Department of Thoracic Surgery, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China.
Department of Respiratory Diseases, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China.
Oncol Lett. 2021 Aug;22(2):591. doi: 10.3892/ol.2021.12852. Epub 2021 Jun 7.
MicroRNAs (miRNAs) are involved in the development of non-small cell lung cancer (NSCLC). However, the biological roles of several aberrantly expressed miRNAs have not been explored yet. In the present study, miR-4491 was identified as a novel upregulated miRNA in NSCLC tissues and cell lines. Downregulation of miR-4491 by a miR-4491 inhibitor inhibited the proliferation and triggered the apoptosis of NSCLC cells. Tripartite motif containing 7 (TRIM7), a tumor suppressor gene expressed in NSCLC, was demonstrated in the present study to be directly targeted by miR-4491. This finding was verified by bioinformatics analysis, reverse transcription-quantitative PCR, western blotting and dual luciferase reporter assays. Furthermore, downregulation of miR-4491 inactivated nuclear factor-κB signaling via induction of TRIM7. In addition, TRIM7 silencing attenuated the effect of miR-4491 inhibitor in NSCLC cells. The decreased TRIM7 level in NSCLC tissues was negatively correlated with miR-4491 expression in NSCLC tissues. In conclusion, the findings from this study demonstrated that miR-4491 expression was upregulated in NSCLC tissues and cells and that miR-4491 may promote NSCLC progression via targeting TRIM7.
微小RNA（miRNA）参与非小细胞肺癌（NSCLC）的发生发展。然而，几种异常表达的miRNA的生物学作用尚未得到探索。在本研究中，miR-4491被鉴定为NSCLC组织和细胞系中一种新的上调miRNA。用miR-4491抑制剂下调miR-4491可抑制NSCLC细胞的增殖并引发其凋亡。含三联基序蛋白7（TRIM7）是一种在NSCLC中表达的肿瘤抑制基因，本研究证明它是miR-4491的直接靶点。这一发现通过生物信息学分析、逆转录定量PCR、蛋白质印迹和双荧光素酶报告基因检测得到验证。此外，miR-4491的下调通过诱导TRIM7使核因子-κB信号失活。此外，TRIM7沉默减弱了miR-4蛋白1抑制剂对NSCLC细胞的作用。NSCLC组织中TRIM7水平的降低与NSCLC组织中miR-4491的表达呈负相关。总之，本研究结果表明，miR-4491在NSCLC组织和细胞中表达上调，且miR-4491可能通过靶向TRIM7促进NSCLC进展。
