Reexpression of Let-7g MicroRNA Inhibits the Proliferation and Migration via K-RasHMGA2Snail Axis in Hepatocellular Carcinoma

Abstract EN

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.