Department of Thoracic Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 201999, P.R. China.
Mol Med Rep. 2020 Oct;22(4):2817-2825. doi: 10.3892/mmr.2020.11373. Epub 2020 Jul 28.
MicroRNA (miRNA/miR)‑92a has been identified as being significantly downregulated in non‑small cell lung cancer (NSCLC) tissues using a miRNA array. However, its biological function and molecular mechanisms in NSCLC have not been fully elucidated. The aim of the present study was to determine the role of miR‑92a in NSCLC and the mechanisms by which it affects NSCLC cells. The expression levels of miR‑92a in NSCLC tissues and cell lines were analyzed using reverse transcription‑quantitative PCR. Cell viability and cell apoptosis were determined using an MTT assay and flow cytometry, respectively. It was observed that miR‑92a was significantly upregulated in NSCLC tissues and cell lines. Inhibition of miR‑92a significantly suppressed viability of NSCLC cells, with concomitant downregulation of key proliferative genes, such as proliferating cell nuclear antigen and Ki‑67. miR‑92a downregulation induced apoptosis of NSCLC cells, as evidenced by flow cytometry and apoptosis‑related protein detection. Luciferase assays confirmed that miR‑92a could directly bind to the 3'‑untranslated region of tumor suppressor F‑box/WD repeat‑containing protein 7 (FBXW7) and suppress its translation. Furthermore, small interfering RNA‑mediated FBXW7 inhibition partially attenuated the tumor suppressive effect of an miR‑92a inhibitor on NSCLC cells. Collectively, these findings demonstrated that miR‑92a might function as an oncogene in NSCLC by regulating FBXW7. In conclusion, miR‑92a could serve as a potential therapeutic target in NSCLC treatment.
微小 RNA(miRNA/miR)-92a 在 miRNA 芯片中被鉴定为在非小细胞肺癌(NSCLC)组织中显著下调。然而,其在 NSCLC 中的生物学功能和分子机制尚未完全阐明。本研究旨在确定 miR-92a 在 NSCLC 中的作用以及其影响 NSCLC 细胞的机制。采用逆转录-定量 PCR 分析 NSCLC 组织和细胞系中 miR-92a 的表达水平。采用 MTT 法和流式细胞术分别测定细胞活力和细胞凋亡。结果观察到,miR-92a 在 NSCLC 组织和细胞系中显著上调。抑制 miR-92a 显著抑制 NSCLC 细胞的活力,同时下调关键增殖基因,如增殖细胞核抗原和 Ki-67。流式细胞术和凋亡相关蛋白检测证实 miR-92a 下调诱导 NSCLC 细胞凋亡。荧光素酶报告基因实验证实 miR-92a 可直接结合肿瘤抑制因子 F-box/WD 重复蛋白 7(FBXW7)的 3'-非翻译区,并抑制其翻译。此外,小干扰 RNA 介导的 FBXW7 抑制部分减弱了 miR-92a 抑制剂对 NSCLC 细胞的肿瘤抑制作用。综上所述,这些发现表明 miR-92a 可能通过调节 FBXW7 在 NSCLC 中发挥致癌基因的作用。总之,miR-92a 可能成为 NSCLC 治疗的潜在治疗靶点。