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Abstract
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 via 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.
Communicated by Ramaswamy H. Sarma
Acknowledgements
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Disclosure statement
No potential competing interest was reported by the authors.