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微小RNA-370通过下调癌基因TRAF4抑制非小细胞肺癌的进展。

MicroRNA-370 inhibits the progression of non-small cell lung cancer by downregulating oncogene TRAF4.

作者信息

Chen Tianjun, Gao Fei, Feng Sifang, Yang Tian, Chen Mingwei

机构信息

Respiratory Department, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.

Ultrasound Department, Hua-shan Central Hospital of Xi'an, Xi'an, Shaanxi, P.R. China.

出版信息

Oncol Rep. 2015 Jul;34(1):461-8. doi: 10.3892/or.2015.3978. Epub 2015 May 13.

Abstract

Lung cancer is the leading cause of cancer-related deaths, of which most can be attributed to non-small cell lung cancer (NSCLC). microRNAs (miRNAs) are a group of small non-coding RNAs that focus on post-transcriptional modification. The present study aimed to investigate the role and function of microRNA-370 (miR-370) in NSCLC and explore the underlying functional mechanisms. We found that miR-370 was significantly downregulated in the tumor tissues of NSCLC patients as well as in NSCLC cell lines. Overexpression of miR-370 by infection of recombinant lentivirus markedly inhibited cell proliferation and promoted cell apoptosis of NSCLC cells. In addition, in vivo tumor formation of NSCLC cells was decreased by miR-370 overexpression. Through bioinformatic analysis, we found that tumor necrosis factor receptor-associated factor 4 (TRAF4), an oncogene as previously reported, was predicted as a putative target gene of miR-370. The direct targeting relationship between miR-370 and the 3'-untranslated region was validated by dual-luciferase reporter assay. Furthermore, overexpression of miR-370 downregulated the protein expression of TRAF4 in the NSCLC cells. Moreover, the growth inhibitory effect of miR-370 overexpression on NSCLC cells was abrogated by TRAF4 overexpression. In conclusion, our results suggest that miR-370 plays an important role in NSCLC by regulating TRAF4 and may be a potential target for the treatment of NSCLC.

摘要

肺癌是癌症相关死亡的主要原因,其中大多数可归因于非小细胞肺癌(NSCLC)。微小RNA(miRNA)是一类专注于转录后修饰的小非编码RNA。本研究旨在探讨微小RNA-370(miR-370)在NSCLC中的作用和功能,并探索其潜在的功能机制。我们发现miR-370在NSCLC患者的肿瘤组织以及NSCLC细胞系中显著下调。通过感染重组慢病毒过表达miR-370可显著抑制NSCLC细胞的增殖并促进其凋亡。此外,miR-370过表达可减少NSCLC细胞的体内肿瘤形成。通过生物信息学分析,我们发现肿瘤坏死因子受体相关因子4(TRAF4),如先前报道的一种癌基因,被预测为miR-370的假定靶基因。通过双荧光素酶报告基因测定验证了miR-370与3'-非翻译区之间的直接靶向关系。此外,miR-370过表达下调了NSCLC细胞中TRAF4的蛋白表达。而且,TRAF4过表达消除了miR-370过表达对NSCLC细胞的生长抑制作用。总之,我们的结果表明miR-370通过调节TRAF4在NSCLC中发挥重要作用,可能是NSCLC治疗的潜在靶点。

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