SNHG16 alleviates pulmonary ischemia-reperfusion injury by promoting the Warburg effect through regulating MTCH2 expression: experimental studies.

Abstract

Background: Pulmonary ischemia-reperfusion injury (PIRI) is a major cause of fatality post-lung transplantation. Though some long non-coding RNAs (lncRNAs) have been studied in acute lung injury (ALI), their effects on PIRI remain undefined. The present study aims to explore the underlying mechanism of small nucleolar RNA host gene 16 (SNHG16) in PIRI.

Methods: PIR mouse and oxygen-glucose deprivation/reoxygenation (OGD/R) cell models were established. Exosomes were extracted from human pulmonary microvascular endothelial cells (HPMECs). Functional and rescue experiments were conducted in OGD/R-exposed HPMECs, OGD/R-exposed pulmonary alveolar epithelial type II cells (AECs), and I/R model mice. The relationships among SNHG16, miR-372-3p/miR-373-3p, and MTCH2 were also verified using dual luciferase reporter assay, RNA pull-down and RIP assay.

Results: SNHG16 was downregulated in OGD/R-exposed HPMECs, and SNHG16 overexpression accelerated proliferation, angiogenesis, and ameliorated mitochondrial respiration in OGD/R-exposed HPMECs. HPMEC-derived exosomal SNHG16 suppressed OGD/R-induced type II AEC injury. SNHG16 ameliorated lung injury in PIR mice. Mechanistically, SNHG16 targeted and negatively regulated miR-372-3p and miR-373-3p expression, and MTCH2, a target gene of miR-372-3p/miR-373-3p. SNHG16 was found to upregulate MTCH2 expression not only in a miR-372-3p and miR-373-3p-dependent manner but also suppress ubiquitination induced MTCH2 degradation.

Conclusions: Our findings revealed that SNHG16 overexpression suppressed OGD/R-induced HPMEC apoptosis by promoting Warburg effect, and HPMEC-derived exosomal SNHG16 alleviated PIRI through the miR-372-3p/miR-373-3p/MTCH2 axis, suggesting that SNHG16 as a therapeutic target for PIRI.