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微小RNA-30a通过靶向Myb相关蛋白B抑制非小细胞肺癌。

MicroRNA-30a suppresses non-small-cell lung cancer by targeting Myb-related protein B.

作者信息

Geng Guo-Jun, Yang Ying-Tao, Jiang Jie, Yu Xiu-Yi, Fa Xian-En

机构信息

Department of Thoracic Surgery, The First Hospital Affiliated to Xiamen University, Xiamen, Fujian 361003, P.R. China.

Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.

出版信息

Exp Ther Med. 2018 Feb;15(2):1633-1639. doi: 10.3892/etm.2017.5559. Epub 2017 Nov 24.

Abstract

Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer mortality worldwide. A growing body of evidence indicates that microRNA (miR) have important and diverse roles in the proliferation, apoptosis and metastasis of human cancer cells. In the present study, the molecular regulation mechanism of miR-30a and its potential target, Myb-related protein B (MYBL2) was investigated in NSCLC. Reverse transcription-quantitative polymerase chain reaction results showed that miR-30a was significantly downregulated in NSCLC tissues compared with adjacent normal tissues (P<0.05). MYBL2 has a putative miR-30a target site in its 3'untranslated region according to previous data, prediction databases and TargetScan software. In the present study, a negative correlation was demonstrated between miR-30a and MYBL2 expression in NSCLC. Direct interaction between miR-30a and MYBL2 was also confirmed via a dual-luciferase reporter assay. miR-30a overexpression inhibited the growth of A549 and H460 cells via MTT and bromodeoxyuridine incorporation assays, whereas miR-30a downregulation promoted cell proliferation. In addition, miR-30a overexpression not only increased cell apoptosis and induced cell cycle arrest in A549 and H460 cell lines, but also attenuated tumor growth, and mRNA and protein expression levels of MYBL2. The present findings suggest that miR-30a may suppress NSCLC by targeting MYBL2.

摘要

非小细胞肺癌(NSCLC)是全球癌症死亡的主要原因之一。越来越多的证据表明,微小RNA(miR)在人类癌细胞的增殖、凋亡和转移中发挥着重要且多样的作用。在本研究中,对miR-30a及其潜在靶标Myb相关蛋白B(MYBL2)在NSCLC中的分子调控机制进行了研究。逆转录定量聚合酶链反应结果显示,与相邻正常组织相比,NSCLC组织中miR-30a显著下调(P<0.05)。根据先前的数据、预测数据库和TargetScan软件,MYBL2在其3'非翻译区有一个假定的miR-30a靶位点。在本研究中,NSCLC中miR-30a与MYBL2表达之间呈负相关。通过双荧光素酶报告基因测定也证实了miR-30a与MYBL2之间的直接相互作用。通过MTT和溴脱氧尿苷掺入试验,miR-30a过表达抑制了A549和H460细胞的生长,而miR-30a下调则促进了细胞增殖。此外,miR-30a过表达不仅增加了A549和H460细胞系中的细胞凋亡并诱导细胞周期停滞,还减弱了肿瘤生长以及MYBL2的mRNA和蛋白表达水平。本研究结果表明,miR-30a可能通过靶向MYBL2抑制NSCLC。

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