Meng Fanlu, Zhang Linlin, Shao Yi, Ma Qing, Lv Hui
Department of Oncology, Tianjin Medical University General Hospital No. 154, Anshan Road, Heping District, Tianjin 300052, P. R. China.
Int J Clin Exp Pathol. 2015 Nov 1;8(11):13853-63. eCollection 2015.
Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related deaths. MicroRNAs (miRNAs) have been reported to be involved in tumorigenesis. However, the underlying mechanisms of microRNA-377 (miR-377) in NSCLC remain unknown. Hence, in the present study, we aimed to explore the role of miR-377 in the development of NSCLC, with identifying its target genes. The results showed that miR-377 expression was significantly decreased in NSCLC tissues as well as in NSCLC cell lines. Moreover, high expression of miR-377 could markedly inhibit the viability, proliferation, migration and invasion of NSCLC cells. The bioinformatics analysis results showed that astrocyte elevated gene-1 (AEG-1), an oncogene as previously reported, was a potential target gene of miR-377, which was further validated by dual-luciferase reporter assay. Besides, the expression of AEG-1 in protein level was decreased by miR-377 overexpression, but not in mRNA level. In addition, AEG-1 overexpression could reverse the inhibitory effects on NSCLC cells caused by miR-377 transfection. In conclusion, our results suggested that miR-377 played an important role in the development of NSCLC by regulating AEG-1 and may be a potential therapeutic target for NSCLC.
非小细胞肺癌（NSCLC）是癌症相关死亡的主要原因。据报道，微小RNA（miRNA）参与肿瘤发生。然而，微小RNA-377（miR-377）在NSCLC中的潜在机制仍不清楚。因此，在本研究中，我们旨在探讨miR-377在NSCLC发生发展中的作用，并鉴定其靶基因。结果显示，miR-377在NSCLC组织和NSCLC细胞系中的表达均显著降低。此外，miR-377的高表达可显著抑制NSCLC细胞的活力、增殖、迁移和侵袭。生物信息学分析结果表明，先前报道的癌基因星形胶质细胞上调基因-1（AEG-1）是miR-377的潜在靶基因，双荧光素酶报告基因检测进一步验证了这一点。此外，miR-377过表达可降低AEG-1的蛋白水平表达，但不影响其mRNA水平。此外，AEG-1过表达可逆转miR-377转染对NSCLC细胞的抑制作用。总之，我们的结果表明，miR-377通过调节AEG-1在NSCLC的发生发展中起重要作用，可能是NSCLC的一个潜在治疗靶点。
