Yan Jing-Jun, Chang Ying, Zhang Yu-Nan, Lin Ju-Sheng, He Xing-Xing, Huang Huan-Jun
Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Oncol Lett. 2017 May;13(5):3118-3126. doi: 10.3892/ol.2017.5826. Epub 2017 Mar 8.
Emerging evidence has indicated that microRNAs (miRNAs) are frequently dysregulated and are fundamental in the pathogenesis of hepatocellular carcinoma (HCC). However, the roles of miR-195 in HCC have not been well elucidated. In the present study, the expression of miR-195 was determined to be markedly downregulated in HCC tissues and cell lines, as compared with normal liver cells. Restoration of miR-195 expression resulted in significant inhibition of the proliferation and tumorigenicity of HCC cells and . Gene expression data and luciferase reporter assays revealed that miR-195 is able to directly inhibit the expression of astrocyte elevated gene 1 (AEG-1) through interaction with its 3' untranslated region. Consistently, an inverse correlation between miR-195 and AEG-1 expression was observed in HCC tissues. Furthermore, the overexpression of AEG-1 was able to partially attenuate the miR-195-induced inhibition of cell growth and promotion of apoptosis. Taken together, these findings indicate that miR-195 functions as a tumor suppressor by inhibiting AEG-1. This pathway may provide new insights into the potential molecular mechanisms of HCC.
新出现的证据表明,微小RNA(miRNA)常常失调,并且在肝细胞癌(HCC)的发病机制中起关键作用。然而,miR-195在HCC中的作用尚未得到充分阐明。在本研究中,与正常肝细胞相比,miR-195在HCC组织和细胞系中的表达明显下调。恢复miR-195的表达导致HCC细胞的增殖和致瘤性受到显著抑制。基因表达数据和荧光素酶报告基因检测显示,miR-195能够通过与其3'非翻译区相互作用直接抑制星形胶质细胞上调基因1(AEG-1)的表达。同样,在HCC组织中观察到miR-195与AEG-1表达呈负相关。此外,AEG-1的过表达能够部分减弱miR-195诱导的细胞生长抑制和凋亡促进作用。综上所述,这些发现表明miR-195通过抑制AEG-1发挥肿瘤抑制作用。该途径可能为HCC潜在的分子机制提供新的见解。