CircTUBD1 Regulates Radiation-induced Liver Fibrosis Response via a circTUBD1/micro-203a-3p/Smad3 Positive Feedback Loop.

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

Knockdown of circTUBD1 not only reduced the expression of α-SMA, as a marker of LX-2 cell activation, but also significantly decreased the levels of hepatic fibrosis molecules, collagen type I alpha 1 (COL1A1), collagen type III alpha 1 (COL3A1), and connective tissue growth factor (CTGF) in a three-dimensional (3D) culture system and RILF model in vivo. 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.

SUBMITTER: Niu H 

PROVIDER: S-EPMC9396324 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature