Cao Yi, Tan Shengxing, Tu Yi, Zhang Guoyang, Liu Yi, Li Daojiang, Xu Shan, Le Zhibiao, Xiong Jianbo, Zou Wenyu, Gong Peitao, Li Zhengrong, Jie Zhigang
Department of General Surgery, First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Department of Pathology, First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Oncol Lett. 2018 Apr;15(4):5119-5130. doi: 10.3892/ol.2018.7983. Epub 2018 Feb 7.
Accumulating studies have demonstrated microRNAs (miRNAs/miRs) have an important role in multiple processes of human malignant tumor development and progression. Decreased expression of miR-125a-5p has been observed in several types of cancer, including gastric cancer (GC). However, the mechanism and exact function of miR-125a-5p in GC have not been largely elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction indicated that the expression of miR-125a-5p was downregulated in GC tissues and cell lines compared with matched normal tissues (P<0.01) and normal gastric mucosa cell lines (P<0.01), respectively. Moreover, clinical pathological characteristics and Kaplan-Meier analysis indicated that a low expression of miR-125a-5p was not only associated with lymph metastasis, peritoneal dissemination and advanced tumor-node metastasis stage but also affected the prognosis of GC patients. Compared with miR-control-transfected GC cells, markedly decreased migration and invasion was observed in GC cells that overexpress miR-125a-5p. By contrast, increased metastasis and invasion were observed in miR-125a-5p-knocked down cells compared with the control. Furthermore, luciferase reporter assays indicated that breast cancer metastasis suppressor 1 (BRMS1) was a direct target of miR-125a-5p. Notably, a positive correlation between the levels of BRMS1 and miR-125a-5p in GC tissues was observed, and BRMS1 expression was indicated to be regulated by miR-125a-5p in GC cells. In conclusion, miR-125a-5p may act as a tumor suppressor by targeting the metastasis-inhibitory gene, BRMS1. The data suggesting that BRMS1 is a potential target gene of miR-125a-5p, may provide novel insight into miRNA regulation of human gene expression, and a useful target for gene therapy of GC.
越来越多的研究表明,微小RNA(miRNA/miR)在人类恶性肿瘤发生发展的多个过程中发挥着重要作用。在包括胃癌(GC)在内的多种癌症中,均观察到miR-125a-5p表达降低。然而,miR-125a-5p在GC中的作用机制及确切功能尚未完全阐明。在本研究中,逆转录定量聚合酶链反应表明,与配对的正常组织(P<0.01)和正常胃黏膜细胞系(P<0.01)相比,miR-125a-5p在GC组织和细胞系中的表达均下调。此外,临床病理特征及Kaplan-Meier分析表明,miR-125a-5p低表达不仅与淋巴转移、腹膜播散及肿瘤-淋巴结转移晚期相关,还影响GC患者的预后。与转染miR对照的GC细胞相比,过表达miR-125a-5p的GC细胞迁移和侵袭能力明显降低。相反,与对照相比,miR-125a-5p敲低的细胞转移和侵袭能力增强。此外,荧光素酶报告基因检测表明,乳腺癌转移抑制因子1(BRMS1)是miR-125a-5p的直接靶点。值得注意的是,在GC组织中观察到BRMS1水平与miR-125a-5p呈正相关,且在GC细胞中BRMS1表达受miR-125a-5p调控。总之,miR-125a-5p可能通过靶向转移抑制基因BRMS1发挥肿瘤抑制作用。这些数据表明BRMS1是miR-125a-5p的潜在靶基因,可能为miRNA调控人类基因表达提供新的见解,也为GC的基因治疗提供有用的靶点。