Circular RNA YAP1 acts as the sponge of microRNA‐21‐5p to secure HK‐2 cells from ischaemia/reperfusion‐induced injury

Abstract

Acute kidney injury (AKI), a kind of syndrome with sudden degradation of renal function, is characterized by loss of urine creatinine. 1 With 7.0% incidence in China, AKI becomes a representative public health matter that ranges from newborns to senior citizens. 2 AKI is divided into pre-kidney, intrinsic and post-kidney, of whose pathophysiology risk factors include inflammatory diseases, 3 traumatism 4 and drug overdose. 5 In addition, ischaemia/reperfusion (I/R) during kidney transplantation also is extremely likely to elicit AKI. 6,7 I/R injury, which results from the inadequate supply of oxygen and nutrients to kidney Abstract Circular RNA YAP1 (circYAP1) was reported to participate in progression of gastric cancer. However, the role of circYAP1 in acute kidney injury (AKI) remains obscure.We attempted to examine the effects of circYAP1 on ischaemia/reperfusion-stimulated renal injury. AKI model was established by treating HK-2 cells in ischaemia/ reperfusion (I/R) environment. CircYAP1 expression in blood of AKI patients and I/Rtreated HK-2 cells was evaluated via RT-qPCR. CCK-8, flow cytometry, ELISA and ROS assay were executed to test the impact of circYAP1 on cell viability, apoptosis, inflammatory cytokines and ROS generation. Bioinformatic analysis was executed to explore miRNA targets. The relativity between circYAP1 and miR-21-5p was verified by RT-qPCR and luciferase assay. The functions of miR-21-5p in I/R-triggered injury were reassessed. PI3K/AKT/mTOR pathway was detected by Western blot. Down-regulated circYAP1 was observed in AKI blood samples and I/R-treated HK-2 cells. CircYAP1 overexpression expedited cell growth and weakened secretion of inflammatory factors and ROS generation in I/R-disposed cells. Besides, we found circYAP1 could sponge to miR-21-5p. Interestingly, miR-21-5p overexpression overturned the repressive effects of circYAP1 on cell injury. Moreover, PI3K/AKT/mTOR pathway was activated by circYAP1 via inhibiting miR-21-5p. We demonstrated that circYAP1 activated PI3K/AKT/mTOR pathway and secured HK-2 cells from I/R injury via sponging miR-21-5p. K E Y W O R D S acute kidney injury, circular RNA YAP1, ischaemia/reperfusion, microRNA-21-5p, PI3K/AKT/ mTOR pathway

Circular RNA circEIF4G2 aggravates renal fibrosis in diabetic nephropathy by sponging miR‐218

“…CircRNA_15698 promotes the accumulation of extracellular matrix‐related proteins by blocking miR‐185 9 . Circular RNA YAP1 was reported to protect the kidney HK‐2 cells from ischaemia/reperfusion injury by acting as a sponge of miR‐21‐5p 19 . It was shown that miR‐218 plays a key regulator in the progression of multiple human cancers, but its effects on DN remain unclear.…”

Long Noncoding RNA/Circular RNA-miRNA-mRNA Axes in Ischemia-Reperfusion Injury

“…Huang et al [ 140 ] reported that the circRNA yes-associated protein 1 (circYAP1) expression was downregulated in AKI patients as well as in I/R-treated HK-2 cells. circYAP1 overexpression promoted cell growth and attenuated the secretion of inflammatory factors and ROS generation in HK-2 cells under I/R treatment.…”

CircRNA_30032 promotes renal fibrosis in UUO model mice via miRNA-96-5p/HBEGF/KRAS axis

“…CircRNAs are competitive endogenous RNAs (ceRNAs) that regulate gene expression by sponging their target miRNAs [ 30 – 32 ]. For example, circular RNA YAP1 protects against ischemic injury by regulating the miRNA-21-5p/PI3K/AKT/mTOR axis [ 33 ]. CircLRP6 was found to act as a sponge for miR-205 to regulate proliferation, oxidative stress, ECM accumulation, and inflammation in mesangial cells [ 34 ].…”