Microrna sequencing analysis in obstructive sleep apnea and depression: Anti-oxidant and maoa-inhibiting effects of mir-15b-5p and mir-92b-3p through targeting ptgs1-nf-κb-sp1 signaling

Yung Che Chen*, Po Yuan Hsu, Mao Chang Su, Ting Wen Chen, Chang Chun Hsiao, Chien Hung Chin, Chia Wei Liou, Po Wen Wang, Ting Ya Wang, Yong Yong Lin, Chiu Ping Lee, Meng Chih Lin

*此作品的通信作者

研究成果: Article同行評審

10 引文 斯高帕斯(Scopus)

摘要

The aim of this study was to identify novel microRNAs related to obstructive sleep apnea (OSA) characterized by intermittent hypoxia with re-oxygenation (IHR) injury. Illumina MiSeq was used to identify OSA-associated microRNAs, which were validated in an independent cohort. The interaction between candidate microRNA and target genes was detected in the human THP-1, HUVEC, and SH-SY5Y cell lines. Next-generation sequencing analysis identified 22 differentially expressed miRs (12 up-regulated and 10 down-regulated) in OSA patients. Enriched predicted target pathways included senescence, adherens junction, and AGE-RAGE/TNF-α/HIF-1α signaling. In the validation cohort, miR-92b-3p and miR-15b-5p gene expressions were decreased in OSA patients, and negatively correlated with an apnea hypopnea index. PTGS1 (COX1) gene expression was increased in OSA patients, especially in those with depression. Transfection with miR-15b-5p/miR-92b-3p mimic in vitro reversed IHR-induced early apoptosis, reactive oxygen species production, MAOA hyperactivity, and up-regulations of their predicted target genes, including PTGS1, ADRB1, GABRB2, GARG1, LEP, TNFSF13B, VEGFA, and CXCL5. The luciferase assay revealed the suppressed PTGS1 expression by miR-92b-3p. Down-regulated miR-15b-5p/miR-92b-3p in OSA patients could contribute to IHR-induced oxidative stress and MAOA hyperactivity through the eicosanoid inflammatory pathway via directly targeting PTGS1-NF-κB-SP1 signaling. Over-expression of the miR-15b-5p/miR-92b-3p may be a new therapeutic strategy for OSA-related depression.

原文English
文章編號1854
期刊Antioxidants
10
發行號11
DOIs
出版狀態Published - 11月 2021

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