Potential regulatory role of miRNA and mRNA link to metabolism affected by chronic intermittent hypoxia

Yanru Duan; Shihan Zhang; Yu Li; Wen Zhao; Pinxue Xie; Xi Zhang; Yunhui Du

doi:10.3389/fgene.2022.963184

Potential regulatory role of miRNA and mRNA link to metabolism affected by chronic intermittent hypoxia

Front Genet. 2022 Sep 6:13:963184. doi: 10.3389/fgene.2022.963184. eCollection 2022.

Authors

Yanru Duan¹, Shihan Zhang², Yu Li³, Wen Zhao⁴, Pinxue Xie⁴, Xi Zhang¹, Yunhui Du⁴

Affiliations

¹ Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
² Beijing Key Laboratory of Pediatric Hematology Ocology, Key Laboratory of Major Diseases in Children, Pediatric Oncology Center, National Center for Children's Health, Ministry of Education, Medical Oncology Department, Beijing Children's Hospital, Capital Medical University, Beijing, China.
³ Center for Coronary Artery Disease, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
⁴ Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

Abstract

Aim: Intermittent hypoxia (IH) is the prominent feature of obstructive sleep apnea (OSA) pathophysiology, which is an in dependent risk factor of cardiovascular complications. The effects of IH on adipocyte metabolism were explored by high-throughput sequencing technology. Methods: Plasma was collected from OSA patients and control group to perform mRNA sequencing. 3T3-L1 cells were differentiated into adipocytes then subjected to a 5%-21% O₂ hypoxic environment (IH) for 24 h. High-throughput sequencing method was used to determine differential mRNA and miRNA patterns in fat cells exposed to IH. We then performed Gene Ontology (GO) analysis, identified relevant KEGG pathways and miRNA-target-pathways. Results: Sequencing data showed that OSA affected the expression of 343 mRNAs in the plasma. At the same time, we found that IH affected the expression of 3034 mRNAs in the adipocytes. In addition, 68 differentially expressed mRNAs were overlapped in plasma from OSA patient and IH-induced adipocyte model. We observe that 68 differential genes could be connected to 49 reciprocally expressed miRNAs. We showed that IH significantly reduced the expression of miR-182-5p and miR-30c-2-3p. KEGG predicted that the function of expressed miR-182-5p and miR-30c-2-3p was enriched to AKT signaling pathway. Notably, IH activated PI3K/AKT pathway in fat cells. Conclusion: Our results demonstrated that IH might induce adipocyte metabolism by regulating miR-182-5p and miR-30c-2-3p.

Keywords: adipocyte; chronic intermittent hypoxia; mRNA; miRNA; obstructive sleep apnea.