Hong Weijun, Du Kaifeng, Zhang Qingqing, Ren Zhiguo, Gao Xiwen
Department of Pulmonary and Critical Care Medicine, Minhang Hospital, Fudan University, Shanghai, China.
Department of Respiratory Medicine, No.971 Hospital of People's Liberation Army Navy, Qingdao, Shandong, China.
J Biomol Struct Dyn. 2025 Mar;43(5):2491-2502. doi: 10.1080/07391102.2023.2301514. Epub 2024 Jan 21.
Circular RNAs (circRNAs) have emerged as regulators of cancer progression, including non-small cell lung cancer (NSCLC). Tanreqing (TRQ), a traditional Chinese medicine, is used clinically for respiratory diseases. RT-qPCR quantified circ-WDR78 expression in NSCLC cells. Cell growth, apoptosis, invasion, and migration were assessed by functional assays. RNA-binding protein immunoprecipitation (RIP), luciferase reporter, and RNA pull-down assays determined the competing endogenous RNA (ceRNA) network of circ-WDR78. The interaction between HIF1α and CD274 (PD-L1) promoter was analyzed by chromatin immunoprecipitation (ChIP). Circ-WDR78 expression was up-regulated in TRQ-treated NSCLC cells. Functionally, circ-WDR78 exhibited anti-tumor effects in these cells. Additionally, circ-WDR78 could also induce reactive oxygen species (ROS) accumulation by down-regulating HIF1α expression, promoting autophagy. Mechanistically, circ-WDR78 destabilizes HIF1α the miR-1265/FBXW8 axis. TRQ-induced exosome secretion from NSCLC cells inhibits PD-L1 expression, preventing immune escape. We found that TRQ-treated NSCLC cells secrete exosomes to transmit circ-WDR78 to untreated NSCLC cells, inhibiting the malignancy of recipient tumor cells. In conclusion, TRQ inhibits NSCLC cell proliferation, invasion, and migration through exosomal circ-WDR78-mediated inactivation of the HIF1α signaling pathway, providing potential insight into TRQ injection for NSCLC treatment.
环状RNA（circRNAs）已成为癌症进展的调节因子，包括非小细胞肺癌（NSCLC）。痰热清（TRQ）是一种中药，临床上用于治疗呼吸系统疾病。RT-qPCR定量检测NSCLC细胞中circ-WDR78的表达。通过功能实验评估细胞生长、凋亡、侵袭和迁移情况。RNA结合蛋白免疫沉淀（RIP）、荧光素酶报告基因和RNA下拉实验确定circ-WDR78的竞争性内源RNA（ceRNA）网络。通过染色质免疫沉淀（ChIP）分析HIF1α与CD274（PD-L1）启动子之间的相互作用。在经TRQ处理的NSCLC细胞中，circ-WDR78表达上调。在功能上，circ-WDR78在这些细胞中表现出抗肿瘤作用。此外，circ-WDR78还可通过下调HIF1α表达诱导活性氧（ROS）积累，促进自噬。机制上，circ-WDR78通过miR-1265/FBXW8轴使HIF1α不稳定。TRQ诱导NSCLC细胞分泌外泌体抑制PD-L1表达，防止免疫逃逸。我们发现，经TRQ处理的NSCLC细胞分泌外泌体将circ-WDR78传递给未处理的NSCLC细胞，抑制受体肿瘤细胞的恶性程度。总之，TRQ通过外泌体circ-WDR78介导的HIF1α信号通路失活抑制NSCLC细胞增殖、侵袭和迁移，为TRQ注射液治疗NSCLC提供了潜在的见解。
