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.

中文翻译：

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顺铂介导的miR-145的下调通过c-Myc转录因子在顺铂耐药的卵巢癌细胞中促进PD-L1的上调。

免疫耐受是癌症患者化疗耐药的主要原因之一。研究表明，程序性细胞死亡配体-1（PD-L1）是癌细胞表达的一种抑制性分子，通过诱导T细胞功能障碍，在免疫耐受中起着重要作用。先前研究中我们的RNA测序结果显示，已知在顺铂耐药性卵巢癌细胞中被顺铂下调的microRNA-145（miR-145）也抑制了基因PD-L1的表达。然而，miR-145参与调节卵巢癌顺铂耐药性中PD-L1表达的机制尚不完全清楚。在这里，我们显示顺铂介导的miR-145下调通过靶向c-Myc转录因子而增加了PD-L1表达，从而诱导T细胞凋亡体外。我们还报告说，miR-145的表达与人卵巢癌组织中PD-L1的表达，恶性等级以及化疗后卵巢癌的复发风险呈负相关。总而言之，我们的发现表明，miR-145 / c-Myc / PD-L1轴有助于卵巢癌顺铂耐药，并支持miR-145可能作为卵巢癌化疗的辅助治疗靶标。