Comprehensive Profiling of Transcriptome and m6A Epitranscriptome Uncovers the Neurotoxic Effects of Yunaconitine on HT22 Cells
Objective: To explore different mRNA transcriptome patterns and RNA N6-methyladenosine (m6A) alteration in yunaconitine (YA)-treated HT22 mouse hippocampal neuron, and uncover the role of abnormal mRNA expression and RNA m6A modification in YA-induced neurotoxicity. Methods: HT22 cells were treated...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2024-10-01
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| Series: | Evolutionary Bioinformatics |
| Online Access: | https://doi.org/10.1177/11769343241290461 |
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| author | Beian Lin Jian Zhang Mengting Chen Xinyue Gao Jiaxin Wen Kun Tian Yajiao Wu Zekai Chen Qiaomei Yang An Zhu Chunhong Du |
| author_facet | Beian Lin Jian Zhang Mengting Chen Xinyue Gao Jiaxin Wen Kun Tian Yajiao Wu Zekai Chen Qiaomei Yang An Zhu Chunhong Du |
| author_sort | Beian Lin |
| collection | DOAJ |
| description | Objective: To explore different mRNA transcriptome patterns and RNA N6-methyladenosine (m6A) alteration in yunaconitine (YA)-treated HT22 mouse hippocampal neuron, and uncover the role of abnormal mRNA expression and RNA m6A modification in YA-induced neurotoxicity. Methods: HT22 cells were treated with 0, 5, 10, and 50 μM of YA for 72 h to evaluate their viability and GSH content. Subsequently, mRNA-seq and MeRIP-seq analyses were performed on HT22 cells treated with 0 and 10 μM YA for 72 h, and molecular docking was used to simulate interactions between YA and differentially expressed m6A regulators. The mitochondrial membrane potential was examined using the JC-10 probe, and RT-qPCR was conducted to verify the expression levels of differentially expressed m6A regulatory factors, as well as to assess alterations in the mRNA expression levels of antioxidant genes. Results: YA treatment significantly reduced the viability of HT22 cells and decreased GSH content. The mRNA-seq analysis obtained 1018 differentially expressed genes, KEGG and GO enrichment results of differentially expressed genes mainly comprise the nervous system development, cholinergic synapse, response to oxidative stress, and mitochondrial inner membrane. A total of 7 differentially expressed m6A regulators were identified by MeRIP-seq. Notably, molecular docking results suggested a stable interaction between YA and most of the differentially expressed m6A regulators. Conclusion: This study showed that YA-induced HT22 cell damage was associated with the increased methylation modification level of target gene m6A and abnormal expression of m6A regulators. |
| format | Article |
| id | doaj-art-2eea402ac2b946efab6fab149d31b00d |
| institution | DOAJ |
| issn | 1176-9343 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Evolutionary Bioinformatics |
| spelling | doaj-art-2eea402ac2b946efab6fab149d31b00d2025-08-20T02:39:16ZengSAGE PublishingEvolutionary Bioinformatics1176-93432024-10-012010.1177/11769343241290461Comprehensive Profiling of Transcriptome and m6A Epitranscriptome Uncovers the Neurotoxic Effects of Yunaconitine on HT22 CellsBeian Lin0Jian Zhang1Mengting Chen2Xinyue Gao3Jiaxin Wen4Kun Tian5Yajiao Wu6Zekai Chen7Qiaomei Yang8An Zhu9Chunhong Du10The Second Affiliated Hospital of Fujian Medical University, Quanzhou, ChinaDepartment of Preventive Medicine, School of Public Health, Fujian Medical University Fuzhou, ChinaKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, ChinaKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, ChinaKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, ChinaKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, ChinaKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, ChinaDepartment of Clinical Medicine, School of Basic Medicine, Fujian Medical University, Fuzhou, ChinaDepartment of Gynecology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, ChinaDepartment of Preventive Medicine, School of Public Health, Fujian Medical University Fuzhou, ChinaThe Second Affiliated Hospital of Fujian Medical University, Quanzhou, ChinaObjective: To explore different mRNA transcriptome patterns and RNA N6-methyladenosine (m6A) alteration in yunaconitine (YA)-treated HT22 mouse hippocampal neuron, and uncover the role of abnormal mRNA expression and RNA m6A modification in YA-induced neurotoxicity. Methods: HT22 cells were treated with 0, 5, 10, and 50 μM of YA for 72 h to evaluate their viability and GSH content. Subsequently, mRNA-seq and MeRIP-seq analyses were performed on HT22 cells treated with 0 and 10 μM YA for 72 h, and molecular docking was used to simulate interactions between YA and differentially expressed m6A regulators. The mitochondrial membrane potential was examined using the JC-10 probe, and RT-qPCR was conducted to verify the expression levels of differentially expressed m6A regulatory factors, as well as to assess alterations in the mRNA expression levels of antioxidant genes. Results: YA treatment significantly reduced the viability of HT22 cells and decreased GSH content. The mRNA-seq analysis obtained 1018 differentially expressed genes, KEGG and GO enrichment results of differentially expressed genes mainly comprise the nervous system development, cholinergic synapse, response to oxidative stress, and mitochondrial inner membrane. A total of 7 differentially expressed m6A regulators were identified by MeRIP-seq. Notably, molecular docking results suggested a stable interaction between YA and most of the differentially expressed m6A regulators. Conclusion: This study showed that YA-induced HT22 cell damage was associated with the increased methylation modification level of target gene m6A and abnormal expression of m6A regulators.https://doi.org/10.1177/11769343241290461 |
| spellingShingle | Beian Lin Jian Zhang Mengting Chen Xinyue Gao Jiaxin Wen Kun Tian Yajiao Wu Zekai Chen Qiaomei Yang An Zhu Chunhong Du Comprehensive Profiling of Transcriptome and m6A Epitranscriptome Uncovers the Neurotoxic Effects of Yunaconitine on HT22 Cells Evolutionary Bioinformatics |
| title | Comprehensive Profiling of Transcriptome and m6A Epitranscriptome Uncovers the Neurotoxic Effects of Yunaconitine on HT22 Cells |
| title_full | Comprehensive Profiling of Transcriptome and m6A Epitranscriptome Uncovers the Neurotoxic Effects of Yunaconitine on HT22 Cells |
| title_fullStr | Comprehensive Profiling of Transcriptome and m6A Epitranscriptome Uncovers the Neurotoxic Effects of Yunaconitine on HT22 Cells |
| title_full_unstemmed | Comprehensive Profiling of Transcriptome and m6A Epitranscriptome Uncovers the Neurotoxic Effects of Yunaconitine on HT22 Cells |
| title_short | Comprehensive Profiling of Transcriptome and m6A Epitranscriptome Uncovers the Neurotoxic Effects of Yunaconitine on HT22 Cells |
| title_sort | comprehensive profiling of transcriptome and m6a epitranscriptome uncovers the neurotoxic effects of yunaconitine on ht22 cells |
| url | https://doi.org/10.1177/11769343241290461 |
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