Circular RNA circUbe2k promotes hepatic fibrosis via sponging miR-149-5p/TGF-β2 axis.
Abundant regulatory genes and complex circuits involving non-coding RNAs (ncRNAs) monitor the formation and development of hepatic fibrosis (HF). Circular RNAs (circRNAs) are a class of RNAs generated from protein coding genes by back-splicing, playing crucial roles in various pathological processes, including HF. However, little is known about mechanisms of action of circRNAs, let alone in HF. In this study, we found circUbe2k enhanced in CCl4 -induced HF mice and LX-2 cells stimulated with TGF-β1, regulating the development of HF. Restraining the expression of circUbe2k inhibited α-SMA and Col1α1 expression in CCl4 -induced HF mice and in LX-2 cells stimulated with TGF-β1. Furthermore, inhibiting circUbe2k expression reduced hepatic stellate cells (HSCs) activation and proliferation in vivo and in vitro. Mechanistically, we demonstrated a direct interaction between circUbe2k and miR-149-5p, which results in the modulation of TGF-β2 expressions. Together, circUbe2k may act as a "catalyst" of HSCs activation and HF through the circUbe2k/miR-149-5p/TGF-β2 axis. Our results provide unprecedented evidence for a significant role for circUbe2k to serve as a potential biomarker for HF therapy.
['Zhu|Sai|S|', 'Chen|Xin|X|', 'Wang|Jia-Nan|JN|', 'Xu|Jin-Jin|JJ|', 'Wang|Ao|A|', 'Li|Juan-Juan|JJ|', 'Wu|Sha|S|', 'Wu|Yuan-Yuan|YY|', 'Li|Xiao-Feng|XF|', 'Huang|Cheng|C|', 'Li|Jun|J|']
D000818:Animals D002251:Carbon Tetrachloride D049109:Cell Proliferation D005786:Gene Expression Regulation D008103:Liver Cirrhosis D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D035683:MicroRNAs D000079962:RNA, Circular D015398:Signal Transduction D053781:Transforming Growth Factor beta2 D044763:Ubiquitin-Conjugating Enzymes
circular RNA circUbe2k hepatic fibrosis miR-149-5p TGF-β2