Hsa_circ_0072765 knockdown inhibits proliferation, activation and migration in transforming growth factor-beta (TGF-β)-induced hepatic stellate cells (HSCs) by the miR-197-3p/TRPV3 axis

Abstract

Background: Circular RNAs (circRNAs) participate in the progression of diverse human diseases. However, the effects of circRNAs on liver fibrosis are limited. In this study, we aimed to investigate the functions of hsa_circ_0072765 in liver fibrosis.

Methods: Transforming growth factor-beta (TGF-β)-treated hepatic stellate cells (HSCs) were used as the cell model of liver fibrosis. Quantitative real-time polymerase chain reaction (qRT-PCR) or western blot was performed to determine the expression of hsa_circ_0072765, microRNA-197-3p (miR-197-3p) and transient receptor potential cation channel subfamily V member 3 (TRPV3). 5'-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry analysis and wound-healing assay were conducted to evaluate cell proliferation, cell cycle and migration. HSC activation was assessed by determining the expression of alpha-smooth muscle actin (α-SMA) and type I collagen alpha 1 (Col1A1). Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were manipulated to analyze the relationship of hsa_circ_0072765, miR-197-3p and TRPV3. The exosome morphology was observed under transmission electron microscopy (TEM).

Results: Hsa_circ_0072765 level was increased in TGF-β-induced HSCs. Hsa_circ_0072765 knockdown inhibited cell proliferation, cell cycle, activation and migration in TGF-β-induced HSCs. Hsa_circ_0072765 sponged miR-197-3p and negatively regulated miR-197-3p expression. MiR-197-3p inhibition reversed the effects of hsa_circ_0072765 knockdown on TGF-β-induced HSC proliferation, cell cycle, activation and migration. In addition, TRPV3 was the target gene of miR-197-3p and miR-197-3p overexpression inhibited TGF-β-treated HSC proliferation, cell cycle, activation and migration by targeting TRPV3. Besides, we found that exosomal hsa_circ_0072765 was increased in TGF-β-treated HSCs.

Conclusion: Hsa_circ_0072765 promoted the progression of TGF-β-treated HSCs by decoying miR-197-3p and upregulating TRPV3.