Chen Wei, Zhuang Xibing, Qi Ruixue, Qiao Tiankui
Department of Oncology, Jinshan Hospital, Fudan University Shanghai 201500, China.
Am J Transl Res. 2019 Jul 15;11(7):4348-4357. eCollection 2019.
MicroRNA-302a-5p (miR-302a-5p) has been implicated in several cancers; however, its role in human non-small cell lung carcinoma (NSCLC) remains unknown. In this study, we showed that miR-302a-5p is downregulated in NSCLC tissues and cell lines. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays showed that overexpression of a miR-302a-5p mimic suppressed NSCLC cell proliferation, which was confirmed by the results of a cell cycle assay. Overexpression of miR-302a-5p also reduced the migration and invasion of NSCLC cells. Additionally, miR-302a-5p overexpression significantly inhibited NSCLC growth and metastasis in a mouse xenograft model. With regard to the underlying mechanism, integrin α6 () mRNA was shown to be a novel target of miR-302a-5p, and overexpression of ITGA6 attenuated the inhibitory effects of miR-302a-5p on the proliferation and migration of NSCLC cells. In clinical NSCLC samples, miR-302a-5p expression was negatively correlated with ITGA6 expression, which was high in the samples. Collectively, these results indicate that miR-302a-5p acts as a tumor suppressor in NSCLC by directly targeting mRNA and may be useful as a theranostic biomarker of NSCLC.
微小RNA-302a-5p（miR-302a-5p）已被证实与多种癌症有关；然而，其在人类非小细胞肺癌（NSCLC）中的作用仍不清楚。在本研究中，我们发现miR-302a-5p在NSCLC组织和细胞系中表达下调。细胞计数试剂盒-8和5-乙炔基-2'-脱氧尿苷检测显示，miR-302a-5p模拟物的过表达抑制了NSCLC细胞的增殖，细胞周期检测结果证实了这一点。miR-302a-5p的过表达还降低了NSCLC细胞的迁移和侵袭能力。此外，miR-302a-5p过表达在小鼠异种移植模型中显著抑制了NSCLC的生长和转移。关于潜在机制，整合素α6（）mRNA被证明是miR-302a-5p的一个新靶点，ITGA6的过表达减弱了miR-302a-5p对NSCLC细胞增殖和迁移的抑制作用。在临床NSCLC样本中，miR-302a-5p表达与ITGA6表达呈负相关，而ITGA6在样本中表达较高。总体而言，这些结果表明，miR-302a-5p通过直接靶向mRNA在NSCLC中发挥肿瘤抑制作用，可能作为NSCLC的治疗诊断生物标志物。
