Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
Mol Med Rep. 2017 Oct;16(4):5007-5014. doi: 10.3892/mmr.2017.7195. Epub 2017 Aug 9.
Lung cancer is one of the leading causes of cancer-associated mortality worldwide. Previous evidence suggested that microRNAs (miRs) exhibit important regulatory roles in tumorigenesis and tumor development, including in non‑small cell lung cancer (NSCLC). The present study investigated the expression of miR‑199b in NSCLC tissues and cell lines, in addition to the biological roles of miR‑199b in the carcinogenesis and progression of NSCLC. The results of the present study demonstrated that miR‑199b expression was decreased in NSCLC tissues and cell lines compared with matched adjacent healthy tissues and a healthy human bronchial epithelial cell line, respectively. An MTT assay demonstrated that the viability of NSCLC cells was decreased by miR‑199b. The migratory and invasive abilities of NSCLC cells were suppressed by miR‑199b overexpression. In addition, zinc finger E‑box‑binding homeobox 1 (ZEB1) was identified to be a novel direct downstream and functional target for miR‑199b in NSCLC, using bioinformatics analysis, luciferase reporter assay, the reverse transcription‑quantitative polymerase chain reaction and western blotting. ZEB1 underexpression mimicked the roles of miR‑199b overexpression in NSCLC cells. In conclusion, the present study demonstrated that miR‑199b was downregulated in NSCLC and acted as a tumor suppressor by targeting ZEB1.
肺癌是全球癌症相关死亡的主要原因之一。先前的证据表明,microRNAs(miRs)在肿瘤发生和发展中发挥着重要的调节作用,包括在非小细胞肺癌(NSCLC)中。本研究调查了 miR-199b 在 NSCLC 组织和细胞系中的表达,以及 miR-199b 在 NSCLC 发生和进展中的生物学作用。本研究的结果表明,与匹配的相邻健康组织和正常人支气管上皮细胞系相比,miR-199b 在 NSCLC 组织和细胞系中的表达降低。MTT 分析表明,miR-199b 降低了 NSCLC 细胞的活力。miR-199b 的过表达抑制了 NSCLC 细胞的迁移和侵袭能力。此外,通过生物信息学分析、荧光素酶报告基因检测、逆转录-定量聚合酶链反应和 Western blot 分析,鉴定锌指 E-框结合同源盒 1(ZEB1)是 miR-199b 在 NSCLC 中的一个新的直接下游和功能靶标。ZEB1 下调模拟了 miR-199b 过表达在 NSCLC 细胞中的作用。综上所述,本研究表明 miR-199b 在 NSCLC 中下调,并通过靶向 ZEB1 发挥肿瘤抑制作用。