Recent studies have shown that miRNAs play vital roles in tumorigenesis. However, their effects on the epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) need to be better understood. Our present study demonstrates that miR-221, which is overexpressed in HCC tissues, promotes EMT in HCC cell lines by targeting a new gene, AdipoR1. First, overexpression of miR-221 was identified in 40 pairs of human HCC tumor and matched normal tissues. Moreover, we found that elevated miR-221 was strongly associated with worse clinicopathologic features in HCC patients. Next, the loss of miR-221 inhibited, but its restoration enhanced, the EMT process in HCC cell lines. Furthermore, bioinformatics software predicted that AdipoR1 would be a direct target of miR-221. We then observed negative regulation of miR-221 on AdipoR1 protein expression, and direct binding between them was further verified using dual-luciferase assays. In addition, knockdown of AdipoR1 resulted in promotion of the EMT in HCC cells, and AdipoR1 overexpression reversed the miR-221-induced EMT. Lastly, we found that the JAK/STAT3 pathway may be involved in the AdipoR1-mediated EMT process. In conclusion, miR-221 acts as a promoter of the EMT process in HCC cells by targeting AdipoR1, and this study highlights the potential effects of miR-221 on the prognosis and treatment of HCC.
Keywords: AdipoR1; Epithelial-mesenchymal transition; Hepatocellular carcinoma; JAK; MiRNAs.
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