Cisplatin-mediated down-regulation of miR-145 contributes to up-regulation of PD-L1 via the c-Myc transcription factor in cisplatin-resistant ovarian carcinoma cells.

Abstract

Immune tolerance is one of the leading causes of chemotherapy resistance in carcinoma cases. Studies have shown that programmed cell death ligand-1 (PD-L1), an inhibitory molecule expressed by cancer cells, plays a significant role in immune tolerance through the induction of T cell dysfunction. The results of our RNA sequencing in previous studies revealed that microRNA-145 (miR-145), which is known to be down-regulated by cisplatin in cisplatin-resistant ovarian cancer cells, also represses gene PD-L1 expression. However, the mechanism by which miR-145 contributes to regulate PD-L1 expression in cisplatin resistance of ovarian cancer is yet to be fully understood. Here, we show that cisplatin-mediated miR-145 down-regulation increased PD-L1 expression via targeting the c-Myc transcription factor, thereby inducing T cell apoptosis in vitro. We also report that expression of miR-145 is negatively correlated with PD-L1 expression in human ovarian cancer tissues, malignant grades and the recurrent risks of ovarian cancer after chemotherapy. In summary, our findings suggest that the miR-145/c-Myc/PD-L1 axis contributes to cisplatin resistance in ovarian cancer and support that miR-145 might act as an adjuvant therapeutic target in chemotherapy of ovarian cancer.