Cisplatin chemotherapy-induced miRNA-210 signaling inhibits hepatocellular carcinoma cell growth.

Abstract

BackgroundChemotherapy has improved the survival of hepatocellular carcinoma (HCC) patients, but the underlying mechanisms are still not fully understood. MicroRNAs (miRNAs) are critical regulators in carcinogenesis and involved in response to cancer therapy. However, the correlation between miRNAs and chemotherapy is not well-established, and the detailed mechanisms and responsive targets remain unclear. Here, we investigated the function and mechanism of miR-210 in HCC chemotherapy with cisplatin.MethodsThis study involved samples from patients after HCC surgery, including tumor and non-tumor liver tissues. Total RNA was extracted from the fresh tissue samples and the levels of miR-210 were assessed by qRT-PCR analysis. Cisplatin treatment was performed in HepG2 and PLC cell lines, and ephrin A3 (EFNA3) levels were determined by Western blotting.ResultsWe observed that miR-210 expression was up-regulated in HCC tissues and correlated with HCC progression. Notably, HCC patients underwent recurrences after chemotherapy showed high levels of miR-210 expression in tumors, indicating that miR-210 might be involved in regulating the chemotherapeutic efficacy. We also demonstrated that cisplatin treatment decreased the expression of miR-210 and increased the expression of miR-210 target EFNA3 in HCC cells. Moreover, miR-210 overexpression prevented the effects of cisplatin and rescued HCC cell growth, and miR-210 inhibition contributed to improved chemosensitivity of cisplatin in HCC cells.ConclusionsOur findings defined a novel mechanism underlying the efficacious effects of cisplatin chemotherapy in HCC, and miR-210-induced EFNA3 signaling might be a potential target of cisplatin in HCC treatment.