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

Wenyong Zhou; Shaohua Wang; Jichun Yang; Qi Shi; Nana Feng; Kaiheng Gao; Wan Posum; Mengkun Shi; Meng Xiang; Meng Shi

doi:10.1097/JS9.0000000000002217

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

Int J Surg. 2025 Jan 9. doi: 10.1097/JS9.0000000000002217. Online ahead of print.

Authors

Wenyong Zhou¹, Shaohua Wang², Jichun Yang³, Qi Shi⁴, Nana Feng⁵, Kaiheng Gao², Wan Posum², Mengkun Shi², Meng Xiang⁶, Meng Shi²

Affiliations

¹ Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of thoracic and cardiovascular surgery, Huashan Hospital, Affiliated with Fudan University, Shanghai, China.
³ China School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Shanghai, China.
⁴ Department of Clinical Medicine, Shanghai Medical College, Fudan University, Shanghai, P.R. China.
⁵ Department of Respiratory and Critical Medicine, Shanghai Eighth People's Hospital Affiliated to Jiang Su University, Shanghai, China.
⁶ Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, and Fudan Zhang Jiang Institute, Shanghai, China.

PMID: 39784903
DOI: 10.1097/JS9.0000000000002217

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 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.