Chen Tianjun, Gao Fei, Feng Sifang, Yang Tian, Chen Mingwei
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.
Oncol Rep. 2015 Jul;34(1):461-8. doi: 10.3892/or.2015.3978. Epub 2015 May 13.
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.
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。