Long non-coding RNA FKSG29 regulates oxidative stress and endothelial dysfunction in obstructive sleep apnea

• Published in: Molecular and cellular biochemistry Vol. 479; no. 10; pp. 2723 - 2740
• Main Authors: Chen, Yung-Che, Hsu, Po-Yuan, Su, Mao-Chang, Chen, Yung-Lung, Chang, Ya‐Ting, Chin, Chien-Hung, Lin, I.-Chun, Chen, Yu-Mu, Wang, Ting-Ya, Lin, Yong-Yong, Lee, Chiu-Ping, Lin, Meng-Chih, Hsiao, Chang-Chun
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2024; Springer Nature B.V
• Subjects: Adult; Antioxidants; Apnea; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cancer Research; Cardiology; CYBB protein; Endothelial cells; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Female; Gene expression; Genes; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Hypertension; Hypoxia; Immunofluorescence; Intercellular adhesion molecule 1; Interleukin 6 receptors; Leukocytes (mononuclear); Life Sciences; Low density lipoprotein; Male; Medical Biochemistry; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Monocytes; NADPH Oxidase 2 - genetics; NADPH Oxidase 2 - metabolism; NADPH Oxidase 5 - genetics; NADPH Oxidase 5 - metabolism; Non-coding RNA; NOX4 protein; Oxidants; Oxidative Stress; Oxidizing agents; Oxygenation; Peripheral blood mononuclear cells; Regulations; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Sleep apnea; Sleep Apnea, Obstructive - genetics; Sleep Apnea, Obstructive - metabolism; Sleep disorders; Subgroups; Superoxide dismutase; THP-1 Cells; Umbilical vein; Up-regulation; Vascular Endothelial Growth Factor A; Vasoactive agents; Intermittent hypoxia; Endothelial dysfunction; FKSG29; miR-23a-3p; Obstructive sleep apnea; Long non-coding RNA
• ISSN: 0300-8177; 1573-4919; 1573-4919
• DOI: 10.1007/s11010-023-04880-3

Altered expressions of pro-/anti-oxidant genes are known to regulate the pathophysiology of obstructive sleep apnea (OSA).We aim to explore the role of a novel long non-coding (lnc) RNA FKSG29 in the development of intermittent hypoxia with re-oxygenation (IHR)-induced endothelial dysfunction in OSA. Gene expression levels of key pro-/anti-oxidant genes, vasoactive genes, and the FKSG29 were measured in peripheral blood mononuclear cells from 12 subjects with primary snoring (PS) and 36 OSA patients. Human monocytic THP-1 cells and human umbilical vein endothelial cells (HUVEC) were used for gene knockout and double luciferase under IHR exposure. Gene expression levels of the FKSG29 lncRNA, NOX2 , NOX5 , and VEGFA genes were increased in OSA patients versus PS subjects, while SOD2 and VEGFB gene expressions were decreased. Subgroup analysis showed that gene expression of the miR-23a-3p, an endogenous competitive microRNA of the FKSG29, was decreased in sleep-disordered breathing patients with hypertension versus those without hypertension. In vitro IHR experiments showed that knock-down of the FKSG29 reversed IHR-induced ROS overt production, early apoptosis, up-regulations of the HIF1A/HIF2A/NOX2/NOX4/NOX5/VEGFA/VEGFB genes, and down-regulations of the VEGFB/SOD2 genes, while the protective effects of FKSG29 knock-down were abolished by miR-23a-3p knock-down. Dual-luciferase reporter assays confirmed that FKSG29 was a sponge of miR-23a-3p, which regulated IL6R directly. Immunofluorescence stain further demonstrated that FKSGH29 knock-down decreased IHR-induced uptake of oxidized low density lipoprotein and reversed IHR-induced IL6R/STAT3/GATA6/ICAM1/VCAM1 up-regulations. The findings indicate that the combined RNA interference may be a novel therapy for OSA-related endothelial dysfunction via regulating pro-/anti-oxidant imbalance or targeting miR-23a-IL6R-ICAM1/VCAM1 signaling.