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miR-770 通过靶向 JMJD6 并调控非小细胞肺癌中的 WNT/β-catenin 通路抑制肿瘤发生和 EMT。

MiR-770 inhibits tumorigenesis and EMT by targeting JMJD6 and regulating WNT/β-catenin pathway in non-small cell lung cancer.

机构信息

Department of Thoracic Surgery, The Fifth Central Hospital of Tianjin, Tianjin 300450, PR China.

Department of Thoracic Surgery, The Fifth Central Hospital of Tianjin, Tianjin 300450, PR China.

出版信息

Life Sci. 2017 Nov 1;188:163-171. doi: 10.1016/j.lfs.2017.09.002. Epub 2017 Sep 4.

Abstract

AIMS

MicroRNAs (miRNAs) plays important role in development and disease, especially in cancer including non-small cell lung cancer (NSCLC). However, the role of miR-770 in NSCLC remains unclear. In this study, we aimed to study the function and mechanism of miR-770 in tumorigenesis of NSCLC.

MAIN METHODS

RT-qPCR was used to measure the expression levels of miR-770 in NSCLC tissues and cells. MTT assay, colony formation assay, flow cytometric analysis and transwell migration and invasion assays were performed to investigate the role of miR-770 in NSCLC cells. Bioinformatics and luciferase reporter analyses were used to demonstrate that whether the Jumonji domain-containing 6 (JMJD6) as a direct target of miR-770. The function of JMJD6 in NSCLC was also investigated. Finally, in vivo animal experiment was used to study whether miR-770 was capable of inhibiting tumor growth by inhibiting JMJD6.

KEY FINDINGS

We first showed that miR-770 was downregulated in NSCLC tissues and cell lines, and the low expression of miR-770 was correlated with poor patient survival in NSCLC patients. miR-770 acted on a tumor suppressor by binding to the 3'UTR of JMJD6 and downregulated its expression in NSCLC cells. This study also demonstrated that JMJD6 played as an oncogene in NSCLC cells. miR-770 overexpression was capable of inhibiting NSCLC tumor growth by inhibiting JMJD6 and its downstream WNT/β-catenin pathway both in vitro and in vivo.

SIGNIFICANCE

The present study indicated that miR-770 functioned as a tumor suppressor and it might be a potential biomarker and therapeutic target in NSCLC.

摘要

目的

微小 RNA(miRNAs)在发育和疾病中发挥重要作用,尤其是在癌症中,包括非小细胞肺癌(NSCLC)。然而,miR-770 在 NSCLC 中的作用尚不清楚。在本研究中,我们旨在研究 miR-770 在 NSCLC 肿瘤发生中的功能和机制。

主要方法

使用 RT-qPCR 测量 NSCLC 组织和细胞中 miR-770 的表达水平。MTT 测定、集落形成测定、流式细胞术分析和 Transwell 迁移和侵袭测定用于研究 miR-770 在 NSCLC 细胞中的作用。生物信息学和荧光素酶报告分析用于证明 JMJD6 是否为 miR-770 的直接靶标。还研究了 JMJD6 在 NSCLC 中的功能。最后,进行体内动物实验以研究 miR-770 是否通过抑制 JMJD6 来抑制肿瘤生长。

主要发现

我们首先表明 miR-770 在 NSCLC 组织和细胞系中下调,并且 miR-770 的低表达与 NSCLC 患者的预后不良相关。miR-770 通过与 JMJD6 的 3'UTR 结合并下调 NSCLC 细胞中的其表达而起肿瘤抑制作用。本研究还表明,JMJD6 在 NSCLC 细胞中起癌基因作用。miR-770 过表达通过抑制 JMJD6 及其下游 WNT/β-catenin 通路,无论是在体外还是体内,都能够抑制 NSCLC 肿瘤的生长。

意义

本研究表明 miR-770 作为肿瘤抑制因子发挥作用,它可能是 NSCLC 的潜在生物标志物和治疗靶标。

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