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
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...
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oai:doaj.org-article:befe855373cd4e1e90ad97646c1188552021-11-25T16:29:53ZMicroRNA 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 Signaling10.3390/antiox101118542076-3921https://doaj.org/article/befe855373cd4e1e90ad97646c1188552021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1854https://doaj.org/toc/2076-3921The 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.Yung-Che ChenPo-Yuan HsuMao-Chang SuTing-Wen ChenChang-Chun HsiaoChien-Hung ChinChia-Wei LiouPo-Wen WangTing-Ya WangYong-Yong LinChiu-Ping LeeMeng-Chih LinMDPI AGarticleobstructive sleep apneamicroRNAnext generation sequencingmiR-92bmiR-15bPTGS1Therapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1854, p 1854 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
obstructive sleep apnea microRNA next generation sequencing miR-92b miR-15b PTGS1 Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
obstructive sleep apnea microRNA next generation sequencing miR-92b miR-15b PTGS1 Therapeutics. Pharmacology RM1-950 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 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 |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Yung-Che Chen |
| title |
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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/befe855373cd4e1e90ad97646c118855 |
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