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环状 RNA 0002722 诱导 YAP 的调控促进口腔鳞状细胞癌对铂类药物的耐药性:维替泊芬治疗的意义。

Circ_0002722-induced regulation of YAP promotes platinum resistance in oral squamous cell carcinoma: Implications for verteporfin therapy.

机构信息

Department of Medicine Research, China Medical University Beigang Hospital, Yunlin, Taiwan.

Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.

出版信息

Biochem Pharmacol. 2024 Nov;229:116460. doi: 10.1016/j.bcp.2024.116460. Epub 2024 Aug 2.

Abstract

Oral squamous cell carcinoma (OSCC) poses a significant public health burden due to its high prevalence and poor prognosis. Platinum resistance is one of the major challenges in OSCC treatment. Yes-associated protein (YAP) has been identified as a pivotal player in OSCC tumorigenesis and progression. Circular RNA (circRNA) has been implicated in chemoresistance in various cancers by regulation the function of microRNA. Nevertheless, the specific mechanisms linking circRNA to YAP expression in OSCC remain poorly understood. In this study, we detected the YAP and circRNA hsa_circ_0002722 (circ_0002722) expression by western blot (WB) and quantitative polymerase chain reaction (qPCR). We found that YAP and circ_0002722 were up-regulated in platinum resistance in OSCC tissues. Furthermore, transfection of circ_0002722 siRNA into platinum-resistant cells revealed that circ_0002722 acted as a regulator of miR-1305, which influenced YAP expression and thereby affected platinum sensitivity. In vivo experiments corroborated the synergistic effects of cisplatin and verteporfin (a YAP inhibitor) in combating platinum resistance. Targeting YAP emerges as a promising therapeutic strategy for addressing platinum resistance in OSCC, with circ_0002722 serving as a potential therapy target and valuable diagnostic marker. These findings shed light on the underlying mechanisms of platinum resistance, paving the way for the development of effective treatment approaches.

摘要

口腔鳞状细胞癌(OSCC)由于其高发率和预后不良,对公众健康构成了重大威胁。铂类耐药性是 OSCC 治疗的主要挑战之一。Yes 相关蛋白(YAP)已被确定为 OSCC 肿瘤发生和进展的关键因素。环状 RNA(circRNA)通过调节 microRNA 的功能参与了多种癌症的化疗耐药性。然而,circRNA 与 YAP 在 OSCC 中的表达之间的具体机制仍知之甚少。在本研究中,我们通过 Western blot(WB)和定量聚合酶链反应(qPCR)检测了 YAP 和 circRNA hsa_circ_0002722(circ_0002722)的表达。我们发现 YAP 和 circ_0002722 在 OSCC 组织中的铂类耐药中上调。此外,将 circ_0002722 siRNA 转染至铂类耐药细胞中,发现 circ_0002722 作为 miR-1305 的调节剂发挥作用,影响 YAP 表达,从而影响铂类敏感性。体内实验证实了顺铂和维替泊芬(YAP 抑制剂)联合对抗铂类耐药的协同作用。靶向 YAP 作为一种有前途的治疗策略,为解决 OSCC 中的铂类耐药问题提供了可能,circ_0002722 作为一种潜在的治疗靶点和有价值的诊断标志物。这些发现揭示了铂类耐药的潜在机制,为开发有效的治疗方法铺平了道路。

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