Comprehensive analysis of m6A methylomes in idiopathic pulmonary arterial hypertension
Idiopathic pulmonary arterial hypertension (IPAH) is a serious and fatal disease. Recently, m6A has been reported to play an important role in the lungs of IPAH patients and experimental pulmonary hypertension models. However, the meaning of m6A mRNAs in the peripheral blood of IPAH patients remains...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2023.2242225 |
| _version_ | 1797678768998842368 |
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| author | Ting Huang Yunhong Zeng Yao Yang Haoqin Fan Youcai Deng Wenjuan Chen Jinqiao Liu Fan Yang Wenfeng Li Yunbin Xiao |
| author_facet | Ting Huang Yunhong Zeng Yao Yang Haoqin Fan Youcai Deng Wenjuan Chen Jinqiao Liu Fan Yang Wenfeng Li Yunbin Xiao |
| author_sort | Ting Huang |
| collection | DOAJ |
| description | Idiopathic pulmonary arterial hypertension (IPAH) is a serious and fatal disease. Recently, m6A has been reported to play an important role in the lungs of IPAH patients and experimental pulmonary hypertension models. However, the meaning of m6A mRNAs in the peripheral blood of IPAH patients remains largely unexplored. We aimed to construct a transcriptome-wide map of m6A mRNAs in the peripheral blood of IPAH patients. M6A RNA Methylation Quantification Kit was utilized to measure the total m6A levels in the peripheral blood of IPAH patients. A combination of MeRIP-seq, RNA-seq and bioinformatics analysis was utilized to select m6A-modified hub genes of IPAH. MeRIP-qPCR and RT-qPCR were used to measure the m6A levels and mRNA levels of TP53, RPS27A, SMAD3 and FoxO3 in IPAH patients. Western blot was performed to assess the protein levels of m6A related regulators and m6A related genes in experimental PH animal models, hypoxia-treated and PDGF-BB induced PASMCs. We found that the total m6A levels were increased in peripheral blood of IPAH patients and verified that m6A levels of RPS27A and SMAD3 were significantly elevated and m6A levels of TP53 and FoxO3 were significantly reduced. The mRNA or protein levels of RPS27A, SMAD3, TP53 and FoxO3 were changed in human blood samples, experimental PH animal models and PDGF-BB induced PASMCs. Moreover, METTL3 and YTHDF1 were increased in the hypoxia induced pulmonary hypertension rat model, hypoxia-treated and PDGF-BB induced PASMCs. These finding suggested that m6A may play an important role in IPAH. |
| first_indexed | 2024-03-11T23:04:58Z |
| format | Article |
| id | doaj.art-9fd0b8ca7cb741f3b7c45a4c18c43b48 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:04:58Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-9fd0b8ca7cb741f3b7c45a4c18c43b482023-09-21T13:23:14ZengTaylor & Francis GroupEpigenetics1559-22941559-23082023-12-0118110.1080/15592294.2023.22422252242225Comprehensive analysis of m6A methylomes in idiopathic pulmonary arterial hypertensionTing Huang0Yunhong Zeng1Yao Yang2Haoqin Fan3Youcai Deng4Wenjuan Chen5Jinqiao Liu6Fan Yang7Wenfeng Li8Yunbin Xiao9Hunan Children’s HospitalHunan Children’s HospitalThe General Hospital of Western Theater Command of PLAHunan Children’s HospitalArmy Medical University (Third Military Medical)Hunan Children’s HospitalHunan Children’s HospitalCentral South UniversityHunan Children’s HospitalHunan Children’s HospitalIdiopathic pulmonary arterial hypertension (IPAH) is a serious and fatal disease. Recently, m6A has been reported to play an important role in the lungs of IPAH patients and experimental pulmonary hypertension models. However, the meaning of m6A mRNAs in the peripheral blood of IPAH patients remains largely unexplored. We aimed to construct a transcriptome-wide map of m6A mRNAs in the peripheral blood of IPAH patients. M6A RNA Methylation Quantification Kit was utilized to measure the total m6A levels in the peripheral blood of IPAH patients. A combination of MeRIP-seq, RNA-seq and bioinformatics analysis was utilized to select m6A-modified hub genes of IPAH. MeRIP-qPCR and RT-qPCR were used to measure the m6A levels and mRNA levels of TP53, RPS27A, SMAD3 and FoxO3 in IPAH patients. Western blot was performed to assess the protein levels of m6A related regulators and m6A related genes in experimental PH animal models, hypoxia-treated and PDGF-BB induced PASMCs. We found that the total m6A levels were increased in peripheral blood of IPAH patients and verified that m6A levels of RPS27A and SMAD3 were significantly elevated and m6A levels of TP53 and FoxO3 were significantly reduced. The mRNA or protein levels of RPS27A, SMAD3, TP53 and FoxO3 were changed in human blood samples, experimental PH animal models and PDGF-BB induced PASMCs. Moreover, METTL3 and YTHDF1 were increased in the hypoxia induced pulmonary hypertension rat model, hypoxia-treated and PDGF-BB induced PASMCs. These finding suggested that m6A may play an important role in IPAH.http://dx.doi.org/10.1080/15592294.2023.2242225n6-methyladenosineidiopathic pulmonary arterial hypertensionmettl3ythdf1tp53rps27afoxo3smad3 |
| spellingShingle | Ting Huang Yunhong Zeng Yao Yang Haoqin Fan Youcai Deng Wenjuan Chen Jinqiao Liu Fan Yang Wenfeng Li Yunbin Xiao Comprehensive analysis of m6A methylomes in idiopathic pulmonary arterial hypertension Epigenetics n6-methyladenosine idiopathic pulmonary arterial hypertension mettl3 ythdf1 tp53 rps27a foxo3 smad3 |
| title | Comprehensive analysis of m6A methylomes in idiopathic pulmonary arterial hypertension |
| title_full | Comprehensive analysis of m6A methylomes in idiopathic pulmonary arterial hypertension |
| title_fullStr | Comprehensive analysis of m6A methylomes in idiopathic pulmonary arterial hypertension |
| title_full_unstemmed | Comprehensive analysis of m6A methylomes in idiopathic pulmonary arterial hypertension |
| title_short | Comprehensive analysis of m6A methylomes in idiopathic pulmonary arterial hypertension |
| title_sort | comprehensive analysis of m6a methylomes in idiopathic pulmonary arterial hypertension |
| topic | n6-methyladenosine idiopathic pulmonary arterial hypertension mettl3 ythdf1 tp53 rps27a foxo3 smad3 |
| url | http://dx.doi.org/10.1080/15592294.2023.2242225 |
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