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Cited by 32Obstructive Sleep Apnea ResearchMicroRNA in disease regulationNeuroscience of respiration and sleep

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

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Chen, Yung-Che, Hsu, Po-Yuan, Su, Mao-Chang, Chin, Chien-Hung, Liou, Chia-Wei, Wang, Ting-Ya, Lin, Yong-Yong, Lee, Chiu Ping +2 more·2020·International Journal of Molecular Sciences
DOI 10.3390/ijms21030999PMC PMC7037842
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Abstract

The purpose of this study is to explore the anti-inflammatory role of microRNAs (miR)-21 and miR-23 targeting the TLR/TNF-α pathway in response to chronic intermittent hypoxia with re-oxygenation (IHR) injury in patients with obstructive sleep apnea (OSA). Gene expression levels of the miR-21/23a, and their predicted target genes were assessed in peripheral blood mononuclear cells from 40 treatment-naive severe OSA patients, and 20 matched subjects with primary snoring (PS). Human monocytic THP-1 cell lines were induced to undergo apoptosis under IHR exposures, and transfected with miR-21-5p mimic. Both miR-21-5p and miR-23-3p gene expressions were decreased in OSA patients as compared with that in PS subjects, while TNF-α gene expression was increased. Both miR-21-5p and miR-23-3p gene expressions were negatively correlated with apnea hypopnea index and oxygen desaturation index, while TNF-α gene expression positively correlated with apnea hypopnea index. In vitro IHR treatment resulted in decreased miR-21-5p and miR-23-3p expressions. Apoptosis, cytotoxicity, and gene expressions of their predicted target genes—including TNF-α, ELF2, NFAT5, HIF-2α, IL6, IL6R, EDNRB, and TLR4—were all increased in response to IHR, while all were reversed with miR-21-5p mimic transfection under IHR condition. The findings provide biological insight into mechanisms by which IHR-suppressed miRs protect cell apoptosis via inhibit inflammation, and indicate that over-expression of the miR-21-5p may be a new therapy for OSA.

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  • Compared with 20 matched subjects with primary snoring, miR-23-3p expression was reduced and its target gene TNF-α was increased in OSA patients (40 samples), demonstrating that miR-23-3p directly targets the TLR/TNF-α pathway to cope with chronic intermittent hypoxia with re-oxygenation injury.

    “Compared with 20 matched subjects with primary snoring (PS), the expression level of miR-23–3p was reduced and its target gene TNF-α was increased in OSA patients (40 samples), demonstrating that miR-23–3p directly targets the TLR/TNF-α pathway to cope with chronic intermittent hypoxia with re-oxygenation (IHR) injury [39].”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [39]

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Authors
Chen, Y.-C., Hsu, P.-Y., Su, M.-C., Chin, C.-H., Liou, C.-W., Wang, T.-Y., Lin, Y.-Y., Lee, C. P., Lin, M.-C., & Hsiao, C.-C.
Affiliations
  • Chang Gung University (TW)
  • Chang Gung University of Science and Technology (TW)
Corresponding author
  • Lin, Meng-Chih
  • Hsiao, Chang-Chun
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-02-03
Volume
21
Issue
3
Pages
999
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms21030999
PMC
PMC7037842
OpenAlex
W3003860534
Cited by
32
References
52
Citations by year
2026: 3 · 2025: 1 · 2024: 8 · 2023: 8 · 2022: 8 · 2021: 4
FWCI
3.01
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Ministry of Science and Technology, Taiwan (NMRPG8F6071-6073/ 105-2314-B-182A-092-MY3)
  • Kaohsiung Chang Gung Memorial Hospital (CMRPG8C1183/CMRPG8G0281/CMRPG8J0581)
Topics
  • Health Sciences › Medicine › Physiology › Obstructive Sleep Apnea Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Keywords
miR-21-5p, miR-23a, obstructive sleep apnea, apoptosis, cytotoxicity, TNF-α, TLR4 signaling, inflammation, miRNA-based therapy, THP-1 cells, peripheral blood mononuclear cells, primary snoring, HIF-2α, NFAT5
MeSH terms
Adult, Hypoxia, Female, Humans, Inflammation, Leukocytes, Mononuclear, Male, Middle Aged, Oxygen, Snoring, Tumor Necrosis Factor-alpha, Signal Transduction, Case-Control Studies, Apoptosis, Sleep Apnea, Obstructive, MicroRNAs, Toll-Like Receptor 4

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