Circ_0000811 acts as a miR-15b sponge and inhibits Prkar2a-mediated JAK2/STAT1 pathway to attenuate cerebral ischemic vertigo
Abstract Circular RNAs (circRNAs) have been noted to express in the brain and thus participate in various diseases related to the central nervous system. However, the potential role of circRNAs in cerebral ischemia (CI)-induced vertigo remains unknown. We initially predicted through bioinformatics a...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-05-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-022-01016-2 |
| _version_ | 1811308230024888320 |
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| author | Rui Huang Weishuai Li Dong Han Yan Gao Dongming Zheng Guorong Bi |
| author_facet | Rui Huang Weishuai Li Dong Han Yan Gao Dongming Zheng Guorong Bi |
| author_sort | Rui Huang |
| collection | DOAJ |
| description | Abstract Circular RNAs (circRNAs) have been noted to express in the brain and thus participate in various diseases related to the central nervous system. However, the potential role of circRNAs in cerebral ischemia (CI)-induced vertigo remains unknown. We initially predicted through bioinformatics analysis the poor expression of circ_0000811 related to CI. A mouse model of CI-induced vertigo was then established, which was validated by measurement of escape latency and medial vestibular nucleus (MVN) blood flow, with NeuN/Annexin counterstaining utilized to detect cell apoptosis in the MVN. An oxygen glucose deprivation (OGD)-exposed neuron-like cell model was further established for in vitro gain- and loss- of function assays, with flow cytometry performed to detect cell apoptosis. The poorly expressed circ_0000811, up-regulated miR-15b expression, and down-regulated Prkar2a expression were observed in both mice with CI-induced vertigo and OGD-exposed cells. Our data then demonstrated that circ_0000811 restoration alleviated CI-induced vertigo in mouse models, and that circ_0000811 acted as a miR-15b sponge to inhibit miR-15b expression. Prkar2a was validated as the target gene of miR-15b. Prkar2a restoration was subsequently revealed to repress OGD-induced neuronal apoptosis through JAK2/STAT1 signaling pathway inactivation. Furthermore, inactivation of the JAK2/STAT1 signaling pathway exerted an anti-apoptotic effect in OGD-induced neurons and an alleviatory effect in mice with CI-induced vertigo with Prkar2a overexpression and circ_0000811 overexpression. Taken together, our work suggests that circ_0000811 is involved in neuronal apoptosis of CI-induced vertigo and may be used as a biomarker for ameliorating CI-induced vertigo. |
| first_indexed | 2024-04-13T09:19:27Z |
| format | Article |
| id | doaj.art-f8520ec00c824607baea025ba6578db6 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-13T09:19:27Z |
| publishDate | 2022-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-f8520ec00c824607baea025ba6578db62022-12-22T02:52:40ZengNature Publishing GroupCell Death Discovery2058-77162022-05-018111110.1038/s41420-022-01016-2Circ_0000811 acts as a miR-15b sponge and inhibits Prkar2a-mediated JAK2/STAT1 pathway to attenuate cerebral ischemic vertigoRui Huang0Weishuai Li1Dong Han2Yan Gao3Dongming Zheng4Guorong Bi5Department of Neurology, Shengjing Hospital of China Medical UniversityDepartment of Neurology, Shengjing Hospital of China Medical UniversityDepartment of Neurology, Shengjing Hospital of China Medical UniversityDepartment of Neurology, Shengjing Hospital of China Medical UniversityDepartment of Neurology, Shengjing Hospital of China Medical UniversityDepartment of Neurology, Shengjing Hospital of China Medical UniversityAbstract Circular RNAs (circRNAs) have been noted to express in the brain and thus participate in various diseases related to the central nervous system. However, the potential role of circRNAs in cerebral ischemia (CI)-induced vertigo remains unknown. We initially predicted through bioinformatics analysis the poor expression of circ_0000811 related to CI. A mouse model of CI-induced vertigo was then established, which was validated by measurement of escape latency and medial vestibular nucleus (MVN) blood flow, with NeuN/Annexin counterstaining utilized to detect cell apoptosis in the MVN. An oxygen glucose deprivation (OGD)-exposed neuron-like cell model was further established for in vitro gain- and loss- of function assays, with flow cytometry performed to detect cell apoptosis. The poorly expressed circ_0000811, up-regulated miR-15b expression, and down-regulated Prkar2a expression were observed in both mice with CI-induced vertigo and OGD-exposed cells. Our data then demonstrated that circ_0000811 restoration alleviated CI-induced vertigo in mouse models, and that circ_0000811 acted as a miR-15b sponge to inhibit miR-15b expression. Prkar2a was validated as the target gene of miR-15b. Prkar2a restoration was subsequently revealed to repress OGD-induced neuronal apoptosis through JAK2/STAT1 signaling pathway inactivation. Furthermore, inactivation of the JAK2/STAT1 signaling pathway exerted an anti-apoptotic effect in OGD-induced neurons and an alleviatory effect in mice with CI-induced vertigo with Prkar2a overexpression and circ_0000811 overexpression. Taken together, our work suggests that circ_0000811 is involved in neuronal apoptosis of CI-induced vertigo and may be used as a biomarker for ameliorating CI-induced vertigo.https://doi.org/10.1038/s41420-022-01016-2 |
| spellingShingle | Rui Huang Weishuai Li Dong Han Yan Gao Dongming Zheng Guorong Bi Circ_0000811 acts as a miR-15b sponge and inhibits Prkar2a-mediated JAK2/STAT1 pathway to attenuate cerebral ischemic vertigo Cell Death Discovery |
| title | Circ_0000811 acts as a miR-15b sponge and inhibits Prkar2a-mediated JAK2/STAT1 pathway to attenuate cerebral ischemic vertigo |
| title_full | Circ_0000811 acts as a miR-15b sponge and inhibits Prkar2a-mediated JAK2/STAT1 pathway to attenuate cerebral ischemic vertigo |
| title_fullStr | Circ_0000811 acts as a miR-15b sponge and inhibits Prkar2a-mediated JAK2/STAT1 pathway to attenuate cerebral ischemic vertigo |
| title_full_unstemmed | Circ_0000811 acts as a miR-15b sponge and inhibits Prkar2a-mediated JAK2/STAT1 pathway to attenuate cerebral ischemic vertigo |
| title_short | Circ_0000811 acts as a miR-15b sponge and inhibits Prkar2a-mediated JAK2/STAT1 pathway to attenuate cerebral ischemic vertigo |
| title_sort | circ 0000811 acts as a mir 15b sponge and inhibits prkar2a mediated jak2 stat1 pathway to attenuate cerebral ischemic vertigo |
| url | https://doi.org/10.1038/s41420-022-01016-2 |
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