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miR-140-3p 通过靶向 Janus 激酶 1 抑制非小细胞肺癌的进展。

miR-140-3p inhibits progression of non-small cell lung cancer by targeting Janus kinase 1.

机构信息

Department of Oncology, Hanchuan City People's Hospital of Wuhan University, Hanchuan, Wuhan 432300, China.

出版信息

J Biosci. 2020;45.

PMID:32345774
Abstract

microRNAs (miRNAs) have gained more attention due to the biological functions in many cancers, including non-small cell lung cancer (NSCLC). However, the roles and the mechanism of miR-140-3p in NSCLC progression remain poorly understood. In this study, the expression levels of miR-140-3p and Janus kinase 1 (JAK1) were measured in NSCLC tissues and cells by quantitative real-time PCR. Cell viability, apoptosis, migration and invasion were detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-trtrazolium bromide, flow cytometry, Western blot or trans-well assay, respectively. Murine xenograft model was conducted to analyze the anti-tumor effect of miR-140-3p in vivo. Interaction between miR-140-3p and JAK1 was probed by luciferase reporter activity and Western blot. We found that miR-140-3p expression was down-regulated and JAK1 expression was increased in NSCLC tissues and cells compared with those in corresponding controls. Moreover, overexpression of miR-140-3p inhibited cell viability, migration and invasion while promoted cell apoptosis in NSCLC cells and suppressed NSCLC xenograft tumor growth . Besides, JAK1 was proved as a target of miR-140-3p and its restoration reversed miR-140-3p-mediated regulatory effect on progression of NSCLC. We concluded that miR-140-3p inhibited NSCLC progression by targeting JAK1, providing a novel avenue for treatment of NSCLC.

摘要

微小 RNA(miRNAs)由于在许多癌症中具有生物学功能而受到更多关注,包括非小细胞肺癌(NSCLC)。然而,miR-140-3p 在 NSCLC 进展中的作用和机制仍知之甚少。在这项研究中,通过定量实时 PCR 测量了 NSCLC 组织和细胞中 miR-140-3p 和 Janus 激酶 1(JAK1)的表达水平。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑、流式细胞术、Western blot 或 Transwell 测定分别检测细胞活力、凋亡、迁移和侵袭。通过建立小鼠异种移植模型在体内分析 miR-140-3p 的抗肿瘤作用。通过荧光素酶报告活性和 Western blot 检测 miR-140-3p 与 JAK1 之间的相互作用。与相应对照相比,我们发现 NSCLC 组织和细胞中的 miR-140-3p 表达下调,JAK1 表达上调。此外,miR-140-3p 的过表达抑制了 NSCLC 细胞中的细胞活力、迁移和侵袭,同时促进了细胞凋亡,并抑制了 NSCLC 异种移植肿瘤的生长。此外,JAK1 被证明是 miR-140-3p 的靶标,其恢复逆转了 miR-140-3p 对 NSCLC 进展的调节作用。我们得出结论,miR-140-3p 通过靶向 JAK1 抑制 NSCLC 进展,为 NSCLC 的治疗提供了新的途径。

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