The Mechanism of Long Non-coding RNA MEG3 for Neurons Apoptosis Caused by Hypoxia: Mediated by miR-181b-12/15-LOX Signaling Pathway
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OBJECTIVE: lncRNAs are recently thought to play a significant role in cellular homeostasis during pathological process of diseases by competing inhibiting miRNA function. The aim of present study was to assess the function of long non-coding RNA (lncRNA) MEG3 and its functional interaction with microRNA-181b in cerebral ischemic infarct of mice and hypoxia-induced neurons apoptosis. METHODS: To address this question, we performed the experiments with in vivo middle cerebral artery occlusion (MCAO) mice model and in vitro oxygen-glucose deprivation (OGD)-cultured neuronal HT22 cell line. Relative expression of MEG3, miR-181b, and 12/15-LOX (lipoxygenase) mRNA was determined using quantitative RT-PCR. Western blot was used to evaluate 12/15-LOX protein expression. TUNEL assay was performed to assess cell apoptosis. RESULTS: In both MCAO mice and OGD-cultured HT22 cell, ischemia, or hypoxia treatment results in a time-dependent increase in MEG3 and 12/15-LOX expression and decrease in miR-181b expression. Knockdown of MEG3 contributes to attenuation of hypoxia-induced apoptosis of HT22 cell. Also, expression level of MEG3 negatively correlated with miR-181b expression and positively correlated with 12/15-LOX expression. In contrary to MEG3, miR-181b overexpression attenuated hypoxia-induced HT22 cell apoptosis, as well as suppressed hypoxia-induced increase in 12/15-LOX expression. By luciferase reporter assay, we concluded that miR-181b directly binds to 12/15-LOX 3'-UTR, thereby negatively regulates 12/15-LOX expression. CONCLUSION: Our data suggested that long non-coding RNA MEG3 functions as a competing endogenous RNA for miR-181b to regulate 12/15-LOX expression in middle cerebral artery occlusion-induced ischemic infarct of brain nerve cells.
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lncRNAs act as competing endogenous RNAs (ceRNAs) by competing for binding to miRNAs.
“increasing experimental evidence has confirmed that lncRNAs act as competing endogenous RNAs (ceRNAs) by competing for binding to miRNAs”
From Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway (2017) · cites this paper as [17]
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- Authors
- Liu, X., Hou, L., Huang, W., Gao, Y., Lv, X., & Tang, J.
- Affiliations
- Shandong University (CN)
- Shandong Academy of Chinese Medicine (CN)
- Corresponding author
- Tang, Jiyou
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2016-09-02
- Volume
- 10
- Pages
- 201-201
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC5009716
- OpenAlex
- W2516980545
- Cited by
- 103
- References
- 26
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 7 · 2023: 7 · 2022: 17 · 2021: 11 · 2020: 11 · 2019: 18 · 2018: 14 · 2017: 9 · 2016: 1
- FWCI
- 5.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Natural Science Foundation of Shandong Province (ZR2013HQ016)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- MEG3, long non-coding RNA, miR-181b, 12/15-lipoxygenase, neuronal apoptosis, hypoxia, cerebral ischemia, middle cerebral artery occlusion, oxygen-glucose deprivation, competing endogenous RNA, microRNA regulation, 3' UTR binding, ischemic stroke
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