Silencing circ‐USP1 protects the renal tubular from kidney injury induced by hypoxia via modulating miR‐194‐5p/DNMT3A axis in acute renal allografts

Recent studies indicate that circular RNAs are involved in dysregulation of kidney injury. Nevertheless, the underlying mechanisms remain largely unclear. Therefore, this study sought to investigate the role of circ‐USP1 in the pathogenesis of early renal allografts. Thirty‐two male C57BL/6J mice aged between 6 and 8 weeks were divided into the sham and allograft groups. Thereafter, the association between miR‐194‐5p, circ‐USP1 and DNMT3A was confirmed using a combination of bioinformatics and the luciferase reporter gene assay. Additionally, the expression of circ‐USP1, miR‐194‐5p and DNMT3A mRNA was detected through qPCR. Afterwards, the Western blot assay was performed to examine the expression of DNMT3A protein. Finally, the TUNEL assay was conducted to determine the rate of apoptosis in DNMT3A cells. The expression of circ‐USP1 increased, while that of miR‐194‐5p decreased in renal allografts. Additionally, silencing circ‐USP1 reduced kidney injuries caused by renal allografts in mice. Moreover, miR‐194‐5p was a target for circ‐USP1, and DNMT3A was a target of miR‐194‐5p. Finally, it was shown that silencing circ‐USP1 reduced DNMT3A expression in the kidney of mice that received renal allografts. Circ‐USP1 functions as a competing endogenous RNA for miR‐194‐5p. This occurs in order to regulate DNMT3A expression in kidney injury induced by hypoxia in acute renal allografts.