Tang Zhaohui, Jiang Yongjun, Ding Sijuan, Jiang Shaohui, Tang Ruoting, Luo Pengfei
Department of Oncology, The Central Hospital of Yongzhou No. 396 Yiyun Road, Yongzhou 425000, Hunan, China.
Am J Transl Res. 2022 Nov 15;14(11):8117-8128. eCollection 2022.
MicroRNAs (miRNAs) have been identified to play a role in the development and progression of lung cancer (LC). As of now, the expression and function of miR-370 in LC are still under investigation. Accordingly, this study explores the role and mechanism of miR-370 in LC.
MiR-370 mimics or inhibitors were used to transfect A549 and NCI-H460 cells to overexpress or inhibit miR-370. The colony formation test and Cell Counting Kit-8 were conducted to detect the cell proliferation activity, and transwell test and wound healing test were conducted to evaluate the cell invasion and migration activities. In addition, the downstream target genes of miR-370 in LC were verified by dual luciferase reporter assay and western blot.
Compared to normal tissues and cell lineslines, the miR-370 expression in LC tissues and cells was decreased greatly. Compared to the negative control group, the up-regulation of miR-370 greatly intensified the apoptosis of NCI-H460 cells and weakened the migration, proliferation, and invasion of the cells. However, compared to the inhibitor-negative control group, the downregulation of miR-370 caused the opposite results. Additionally, SMAD family member 1 (SMAD1) was identified as a direct target of miR-370 in LC and could be inhibited by miR-370. Its overexpression restored the impact of miR-370 mimics on LC cells.
With low expression in LC tissues and cell lineslines, miR-370 is a tumor suppressor that weakens the growth, invasion as well as migration of LC cells by inhibiting SMAD1 expression. Our results may provide novel insights for the biological treatment of LC.
微小RNA(miRNA)已被证实参与肺癌(LC)的发生发展过程。目前,miR-370在肺癌中的表达及功能仍在研究中。因此,本研究旨在探讨miR-370在肺癌中的作用及机制。
使用miR-370模拟物或抑制剂转染A549和NCI-H460细胞,以过表达或抑制miR-370。通过集落形成试验和细胞计数试剂盒-8检测细胞增殖活性,通过Transwell试验和伤口愈合试验评估细胞侵袭和迁移活性。此外,通过双荧光素酶报告基因检测和蛋白质印迹法验证miR-370在肺癌中的下游靶基因。
与正常组织和细胞系相比,肺癌组织和细胞中miR-370的表达显著降低。与阴性对照组相比,miR-370的上调显著增强了NCI-H460细胞的凋亡,并减弱了细胞的迁移、增殖和侵袭能力。然而,与抑制剂阴性对照组相比,miR-370的下调则产生了相反的结果。此外,SMAD家族成员1(SMAD1)被确定为miR-370在肺癌中的直接靶标,且可被miR-370抑制。其过表达恢复了miR-370模拟物对肺癌细胞的影响。
miR-370在肺癌组织和细胞系中低表达,是一种肿瘤抑制因子,通过抑制SMAD1表达减弱肺癌细胞的生长、侵袭和迁移能力。我们的研究结果可能为肺癌的生物治疗提供新的见解。