Background/Aims: MicroRNAs (miRNAs) play critical roles during carcinogenesis and cancer progression. Down-regulation of miR-204 has been frequently observed in various cancers. In this study, we investigated the roles and mechanisms of miR-204 in human intrahepatic cholangiocarcinoma (ICC). Methods: The relative expression of miR-204 in ICC tissues and cell lines was monitored by qRT-PCR. Effects of miR-204 were studied in human ICC cell lines HuH28 and HuCCT1, and cells were analyzed for proliferation, migration and invasion. Expression levels of miR-204 target gene Slug and EMT markers (E-cadherin and vimentin) in ICC cell lines and tissues were measured by qRT-PCR, western blotting and immunofluorescence. Results: miR-204 was frequently downregulated in human ICC, and the low-level expression of miR-204 was significantly associated with lymph node metastasis. Overexpression of miR-204 dramatically suppressed ICC cell migration and invasion, as well as the epithelial-mesenchymal transition process (EMT). Slug was identified as a direct target of miR-204, and its downregulation by miR-204 in HuH28 cells reversed EMT, as shown by the increased expression of the epithelial marker E-cadherin and decreased expression of the mesenchymal marker vimentin. Conclusion: These findings suggest that miR-204 plays negative roles in the invasive and/or metastatic potential of ICC, and that its suppressive effects are mediated by repressing Slug expression.

miR-182 is an important mediator of GBC metastasis, thus offering a new target for the development of therapeutic agents against GBC.

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Angiogenesis is a fundamental part of the response to tissue injury, which is involved in the development of hepatic fibrosis. Vascular endothelial growth factor plays an important role in angiogenesis. The expression of VEGF is increased during hepatic fibrogenesis and correlates with the micro-vessel density. In this study, we investigated the effects of bevacizumab, an anti-angiogenetic drug, on the formation of hepatic fibrosis. We found that bevacizumab could attenuate the development of hepatic fibrosis and contribute to the protection of liver function. Bevacizumab was also found to downregulate the expression α-SMA and TGF-β1, which have been reported to be profibrogenic genes in vivo. We also observed that the expression of VEGF increased significantly during the development of hepatic fibrosis and CCl4 was found to induce hepatocytes to secrete VEGF, which led to the activation and proliferation of HSCs. Bevacizumab was also found to block the effects of the hepatocytes on the activation and proliferation of HSCs. Our results suggest that bevacizumab might alleviate liver fibrosis by blocking the effect of VEGF on HSCs. Bevacizumab might be suitable as a potential agent for hepatic fibrosis therapy.

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