CircTUBD1 Regulates Radiation-induced Liver Fibrosis Response via a circTUBD1/micro-203a-3p/Smad3 Positive Feedback Loop
Hao Niu, Li Zhang, Biao Wang, Guangcong Zhang, Juan Liu, Zhifeng Wu, Shisuo Du, Zhao‐Chong Zeng
Abstract
Background and Aims: Radiation-induced liver fibrosis (RILF), delayed damage to the liver (post-irradiation) remains a major challenge for the radiotherapy of liver malignancies. This study investigated the potential function and mechanism of circTUBD1 in the development of RILF. Methods: By using a dual luciferase assay, RNA pull-down assays, RNA sequencing, chromatin immunoprecipitation (known as ChIP) assays, and a series of gain- or loss-of-function experiments, it was found that circTUBD1 regulated the activation and fibrosis response of LX-2 cells induced by irradiation via a circTUBD1/micro-203a-3p/Smad3 positive feedback loop in a 3D system. Results: . Notably, knockdown of circTUBD1 alleviated early liver fibrosis induced by irradiation in mice models. Conclusions: This study is the first to reveal the mechanism and role of circTUBD1 in RILF via a circTUBD1/micro-203a-3p/Smad3 feedback loop, which provides a novel therapeutic strategy for relieving the progression of RILF.