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




Reexpression of Let-7g MicroRNA Inhibits the Proliferation and Migration via K-Ras-HMGA2-Snail Axis in Hepatocellular Carcinoma - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BioMed Research InternationalVolume 2014 2014, Article ID 742417, 12 pages

Research ArticleDepartment of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, China

Received 9 December 2013; Revised 16 January 2014; Accepted 26 January 2014; Published 4 March 2014

Academic Editor: Chunping Jiang

Copyright © 2014 Ke-ji Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.





Autor: Ke-ji Chen, Ying Hou, Kui Wang, Jun Li, Yong Xia, Xiao-yu Yang, Gang Lv, Xiang-Lei Xing, and Feng Shen

Fuente: https://www.hindawi.com/



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