Reexpression of Let-7g MicroRNA Inhibits the Proliferation and Migration via K-Ras/HMGA2/Snail Axis in Hepatocellular Carcinoma

• Published in: BioMed research international 2014-01, Vol.2014 (2014), p.1-12
• Main Authors: Chen, Ke-ji, Hou, Ying, Wang, Kui, Li, Jun, Xia, Yong, Yang, Xiao-yu, Lv, Gang, Xing, Xiang-Lei, Shen, Feng
• Format: Article
• Language: English
• Subjects: Animals; Breast cancer; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; Cell adhesion & migration; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Gene expression; Gene Expression Regulation, Neoplastic; HMGA2 Protein - genetics; HMGA2 Protein - metabolism; Humans; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Male; Medical prognosis; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - biosynthesis; MicroRNAs - genetics; Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; ras Proteins - metabolism; RNA, Neoplasm - biosynthesis; RNA, Neoplasm - genetics; Rodents; Snail Family Transcription Factors; Surgery; Thermal cycling; Transcription Factors - genetics; Transcription Factors - metabolism; Tumorigenesis; Tumors
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2014/742417

Let-7 family microRNAs have been reported to be downregulated in human hepatocellular carcinoma in comparison with normal hepatic tissues. Among them, let-7g was identified as the lowest expression using real-time RT-PCR. However, the mechanism by which let-7g works in hepatocellular carcinoma remains unknown. Here, in our present study, we have had let-7g reexpressed in vitro in hepatocellular carcinoma cell lines MHCC97-H and HCCLM3 via transfection. The proliferation after reexpression of let-7g was assayed using MTT method; the migration and invasion after restoration were detected by wound-healing and Transwell assay, respectively. We found using Western-blotting that let-7g can regulate epithelial-mesenchymal transition (EMT) by downregulating K-Ras and HMGA2A after reexpresssion. Xenografted nude mice were used to observe whether or not reexpression of let-7g could have potential therapeutic ability. In vivo, to observe the association with let-7g expression and overall prognosis, 40 paired cases of hepatocellular carcinoma were analyzed using in situ hybridization (ISH). It was found that reexpression of let-7g can inhibit the proliferation, migration, and invasion significantly, and that low expression of let-7g was significantly associated with poorer overall survival. Taken together, let-7g could be used as a promising therapeutic agent in vivo in the treatment of hepatocellular carcinoma at the earlier stage.