A Novel lncRNA MSTRG .16386.1 as ceRNA Promotes Kidney Injury Induced by Deep Hypothermic Circulatory Arrest via Mediating miR ‐466b‐5p/Spry2 Axis

Kidney injury is a common complication of deep hypothermic circulatory arrest (DHCA) in patients undergoing cardiac surgery. However, the role of competitive endogenous RNA (ceRNA) networks in mediating DHCA-induced kidney injury has not been fully elucidated. In the present study, we aimed to systematically analyze ceRNA networks and identify a novel lncRNA, MSTRG.16386.1, that promotes DHCA-induced kidney injury by regulating the miR-466b-5p/Sprouty RTK signaling antagonist 2 (Spry2) axis. Kidney injury induced by DHCA was confirmed using a rat model of cardiopulmonary bypass (CPB) with or without DHCA. In addition, lncRNA and mRNA sequencing of kidney tissues revealed 309 specific shared differentially expressed mRNAs (DEGs) and 439 differentially expressed lncRNAs (DELs) in the kidneys of CPB+DHCA rats compared with those of SHAM and CPB rats. Differentially expressed miRNAs (DEMs) were predicted by coexpression and binding site analysis. A ceRNA network consisting of 12 DEGs, 6 DELs, and 11 DEMs was constructed, and the top ranked RNAs were Sprouty RTK Signaling Antagonist 2 (Spry2), MSTRG.16386.1, and miR-466b-5p, which were verified using qRT-PCR. We found that MSTRG.16386.1 overexpression resulted in NRK-52E cell apoptosis, which was suppressed by the interaction with miR-466b-5p. In addition, we demonstrated that Spry2 is a key target of MSTRG.16386.1 and miR-466b-5p. Rescue experiment results revealed that the downregulated expression of Spry2 protected NRK-52E cells against apoptosis mediated by MSTRG.16386.1 overexpression or an miR-466b-5p inhibitor. Our findings provide novel insights into ceRNA regulation of the MSTRG.16386.1/miR-466b-5p/Spry2 axis in DHCA-induced kidney injury by the induction of apoptosis.