miR-375/Yes-associated protein axis regulates IL-6 and TGF-[beta] expression, which is involved in the cisplatin-induced resistance of liver cancer cells

Chemotherapy resistance is one of the major challenges in the treatment of liver cancer (LC). The present study aimed to investigate the potential roles of Yes-associated protein (YAP), the core component of the Hippo signaling pathway, in chemoresistance of LC. YAP expression and its function in chemoresistance of LC cells were investigated. It was revealed that the expression levels and nuclear localization of YAP were increased in cisplatin (CDDP)-resistant LC (LC/CDDP) cells. The targeted inhibition of YAP using small interfering RNA or an inhibitor restored the CDDP sensitivity of LC cells. YAP overexpression was discovered to be essential for the increase of IL-6 and TGF-[beta] expression levels in LC/CDDP cells. Furthermore, it was identified that increased mRNA stability was the primary reason for the upregulation of YAP expression in LC/CDDP cells, which was due to the downregulation of microRNA (miR)-375 expression in LC/CDDP cells. In conclusion, the findings of the present study suggested that the miR-375/YAP axis may regulate the expression levels of IL-6 and TGF-[beta], which may subsequently be involved in the CDDP resistance of LC cells. The current results indicated that the targeted inhibition of this axis and signaling pathway may be helpful in overcoming CDDP resistance. Key words: liver cancer, cisplatin, resistance, Yes-associated protein, microRNA-375