Circular RNA cVIM promotes hepatic stellate cell activation in liver fibrosis via miR-122-5p/miR-9-5p-mediated TGF-β signaling cascade
Zhenxu Zhou, Rongrong Zhang, Xinmiao Li, Weizhi Zhang, Yating Zhan, Zhichao Lang, Qiqi Tao, Jinglu Yu, Suhui Yu, Zhengping Yu, Jianjian Zheng
Abstract
Hepatic stellate cell (HSC) activation is considered as a central driver of liver fibrosis and effective suppression of HSC activation contributes to the treatment of liver fibrosis. Circular RNAs (circRNAs) have been reported to be important in tumor progression. However, the contributions of circRNAs in liver fibrosis remain largely unclear. The liver fibrosis-specific circRNA was explored by a circRNA microarray and cVIM (a circRNA derived from exons 4 to 8 of the vimentin gene mmu_circ_32994) was selected as the research object. Further studies revealed that cVIM, mainly expressed in the cytoplasm, may act as a sponge for miR-122-5p and miR-9-5p to enhance expression of type I TGF-β receptor (TGFBR1) and TGFBR2 and promotes activation of the TGF-β/Smad pathway, thereby accelerating the progression of liver fibrosis. Our results demonstrate a vital role for cVIM in promoting liver fibrosis progression and provide a fresh perspective on circRNAs in liver fibrosis.