Comprehensive analyses of m6A RNA methylation patterns and related immune microenvironment in idiopathic pulmonary arterial hypertension
Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease with a poor prognosis and high heritability, characterized by elevated pulmonary vascular resistance (PVR) and pulmonary artery pressure. N6-methyladenosine (m6A) RNA modification influences many RNA metabolism pathways....
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1222368/full |
| _version_ | 1797693121997307904 |
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| author | Gufeng Gao Gufeng Gao Gufeng Gao Gufeng Gao Gufeng Gao Ai Chen Ai Chen Ai Chen Ai Chen Ai Chen Jin Gong Jin Gong Jin Gong Jin Gong Jin Gong Weijun Lin Weijun Lin Weijun Lin Weijun Lin Weijun Lin Weibin Wu Weibin Wu Weibin Wu Weibin Wu Weibin Wu Sagor Mohammad Ismail Hajary Sagor Mohammad Ismail Hajary Sagor Mohammad Ismail Hajary Sagor Mohammad Ismail Hajary Sagor Mohammad Ismail Hajary Guili Lian Guili Lian Guili Lian Guili Lian Guili Lian Li Luo Li Luo Li Luo Li Luo Li Luo Liangdi Xie Liangdi Xie Liangdi Xie Liangdi Xie Liangdi Xie |
| author_facet | Gufeng Gao Gufeng Gao Gufeng Gao Gufeng Gao Gufeng Gao Ai Chen Ai Chen Ai Chen Ai Chen Ai Chen Jin Gong Jin Gong Jin Gong Jin Gong Jin Gong Weijun Lin Weijun Lin Weijun Lin Weijun Lin Weijun Lin Weibin Wu Weibin Wu Weibin Wu Weibin Wu Weibin Wu Sagor Mohammad Ismail Hajary Sagor Mohammad Ismail Hajary Sagor Mohammad Ismail Hajary Sagor Mohammad Ismail Hajary Sagor Mohammad Ismail Hajary Guili Lian Guili Lian Guili Lian Guili Lian Guili Lian Li Luo Li Luo Li Luo Li Luo Li Luo Liangdi Xie Liangdi Xie Liangdi Xie Liangdi Xie Liangdi Xie |
| author_sort | Gufeng Gao |
| collection | DOAJ |
| description | Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease with a poor prognosis and high heritability, characterized by elevated pulmonary vascular resistance (PVR) and pulmonary artery pressure. N6-methyladenosine (m6A) RNA modification influences many RNA metabolism pathways. However, the position of m6A methylation regulators in IPAH remains unknown. Therefore, the study aims to disclose the function m6A regulators exert in the pathological mechanisms of IPAH and the immune microenvironment involved. The GSE117261 dataset was downloaded from the Gene Expression Omnibus (GEO) to screen the differentially expressed genes (DEGs) between normal and IPAH samples. Functional and pathway enrichment analyses of DEGs were then conducted by Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG). We also identified the differentially-expressed m6A (DEm6A) regulators between normal and IPAH samples. Key m6A regulators related to the prediction of IPAH were selected using the random forest model. The results showed that FMR1, RBM15, HNRNPA2B1 and IGFBP3 were upregulated in IPAH. In contrast, LRPPRC was downregulated. The single sample gene set enrichment analysis (ssGSEA) method was then adopted to estimate the immune microenvironment in distinct m6A clusters and m6A phenotype-related genes (PRGs) clusters, respectively. Furthermore, we calculated the m6A score via principal component analysis (PCA), and the Sankey diagram was selected to present the correlation among the m6A clusters, m6A PRGs clusters and m6A score. Finally, quantitative RT-PCR and Western blotting were used to validate the key genes in human pulmonary artery smooth muscle cells (HPASMCs) treated by human platelet-derived growth factor-BB (PDGF-BB). The relative mRNA and protein expression levels of FMR1 were significantly elevated, however, the relative mRNA and protein expression levels of LRPPRC were downregulated. Besides, the relative mRNA level of HNRNPA2B1 was increased. Generally, this bioinformatics analysis might provoke more insights into diagnosing and treating IPAH. |
| first_indexed | 2024-03-12T02:39:00Z |
| format | Article |
| id | doaj.art-12241b3ee01d4687a91c9c15dc4210fe |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-12T02:39:00Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-12241b3ee01d4687a91c9c15dc4210fe2023-09-04T09:22:47ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-09-011410.3389/fgene.2023.12223681222368Comprehensive analyses of m6A RNA methylation patterns and related immune microenvironment in idiopathic pulmonary arterial hypertensionGufeng Gao0Gufeng Gao1Gufeng Gao2Gufeng Gao3Gufeng Gao4Ai Chen5Ai Chen6Ai Chen7Ai Chen8Ai Chen9Jin Gong10Jin Gong11Jin Gong12Jin Gong13Jin Gong14Weijun Lin15Weijun Lin16Weijun Lin17Weijun Lin18Weijun Lin19Weibin Wu20Weibin Wu21Weibin Wu22Weibin Wu23Weibin Wu24Sagor Mohammad Ismail Hajary25Sagor Mohammad Ismail Hajary26Sagor Mohammad Ismail Hajary27Sagor Mohammad Ismail Hajary28Sagor Mohammad Ismail Hajary29Guili Lian30Guili Lian31Guili Lian32Guili Lian33Guili Lian34Li Luo35Li Luo36Li Luo37Li Luo38Li Luo39Liangdi Xie40Liangdi Xie41Liangdi Xie42Liangdi Xie43Liangdi Xie44Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaClinical Research Center for Geriatric Hypertension Disease of Fujian Province, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaBranch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, ChinaDepartment of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fujian, Fuzhou, ChinaDepartment of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaClinical Research Center for Geriatric Hypertension Disease of Fujian Province, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaBranch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, ChinaDepartment of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fujian, Fuzhou, ChinaDepartment of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaClinical Research Center for Geriatric Hypertension Disease of Fujian Province, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaBranch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, ChinaDepartment of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fujian, Fuzhou, ChinaDepartment of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaClinical Research Center for Geriatric Hypertension Disease of Fujian Province, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaBranch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, ChinaDepartment of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fujian, Fuzhou, ChinaDepartment of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaClinical Research Center for Geriatric Hypertension Disease of Fujian Province, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaBranch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, ChinaDepartment of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fujian, Fuzhou, ChinaDepartment of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaClinical Research Center for Geriatric Hypertension Disease of Fujian Province, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaBranch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, ChinaDepartment of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fujian, Fuzhou, ChinaDepartment of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaClinical Research Center for Geriatric Hypertension Disease of Fujian Province, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaBranch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, ChinaDepartment of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fujian, Fuzhou, ChinaDepartment of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaClinical Research Center for Geriatric Hypertension Disease of Fujian Province, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaBranch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, ChinaDepartment of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fujian, Fuzhou, ChinaDepartment of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaClinical Research Center for Geriatric Hypertension Disease of Fujian Province, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou, ChinaBranch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, ChinaDepartment of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fujian, Fuzhou, ChinaIdiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease with a poor prognosis and high heritability, characterized by elevated pulmonary vascular resistance (PVR) and pulmonary artery pressure. N6-methyladenosine (m6A) RNA modification influences many RNA metabolism pathways. However, the position of m6A methylation regulators in IPAH remains unknown. Therefore, the study aims to disclose the function m6A regulators exert in the pathological mechanisms of IPAH and the immune microenvironment involved. The GSE117261 dataset was downloaded from the Gene Expression Omnibus (GEO) to screen the differentially expressed genes (DEGs) between normal and IPAH samples. Functional and pathway enrichment analyses of DEGs were then conducted by Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG). We also identified the differentially-expressed m6A (DEm6A) regulators between normal and IPAH samples. Key m6A regulators related to the prediction of IPAH were selected using the random forest model. The results showed that FMR1, RBM15, HNRNPA2B1 and IGFBP3 were upregulated in IPAH. In contrast, LRPPRC was downregulated. The single sample gene set enrichment analysis (ssGSEA) method was then adopted to estimate the immune microenvironment in distinct m6A clusters and m6A phenotype-related genes (PRGs) clusters, respectively. Furthermore, we calculated the m6A score via principal component analysis (PCA), and the Sankey diagram was selected to present the correlation among the m6A clusters, m6A PRGs clusters and m6A score. Finally, quantitative RT-PCR and Western blotting were used to validate the key genes in human pulmonary artery smooth muscle cells (HPASMCs) treated by human platelet-derived growth factor-BB (PDGF-BB). The relative mRNA and protein expression levels of FMR1 were significantly elevated, however, the relative mRNA and protein expression levels of LRPPRC were downregulated. Besides, the relative mRNA level of HNRNPA2B1 was increased. Generally, this bioinformatics analysis might provoke more insights into diagnosing and treating IPAH.https://www.frontiersin.org/articles/10.3389/fgene.2023.1222368/fullidiopathic pulmonary arterial hypertensionm6A methylation regulatorsimmune microenvironmenthuman pulmonary artery smooth muscle cellsplatelet-derived growth factor-BB |
| spellingShingle | Gufeng Gao Gufeng Gao Gufeng Gao Gufeng Gao Gufeng Gao Ai Chen Ai Chen Ai Chen Ai Chen Ai Chen Jin Gong Jin Gong Jin Gong Jin Gong Jin Gong Weijun Lin Weijun Lin Weijun Lin Weijun Lin Weijun Lin Weibin Wu Weibin Wu Weibin Wu Weibin Wu Weibin Wu Sagor Mohammad Ismail Hajary Sagor Mohammad Ismail Hajary Sagor Mohammad Ismail Hajary Sagor Mohammad Ismail Hajary Sagor Mohammad Ismail Hajary Guili Lian Guili Lian Guili Lian Guili Lian Guili Lian Li Luo Li Luo Li Luo Li Luo Li Luo Liangdi Xie Liangdi Xie Liangdi Xie Liangdi Xie Liangdi Xie Comprehensive analyses of m6A RNA methylation patterns and related immune microenvironment in idiopathic pulmonary arterial hypertension Frontiers in Genetics idiopathic pulmonary arterial hypertension m6A methylation regulators immune microenvironment human pulmonary artery smooth muscle cells platelet-derived growth factor-BB |
| title | Comprehensive analyses of m6A RNA methylation patterns and related immune microenvironment in idiopathic pulmonary arterial hypertension |
| title_full | Comprehensive analyses of m6A RNA methylation patterns and related immune microenvironment in idiopathic pulmonary arterial hypertension |
| title_fullStr | Comprehensive analyses of m6A RNA methylation patterns and related immune microenvironment in idiopathic pulmonary arterial hypertension |
| title_full_unstemmed | Comprehensive analyses of m6A RNA methylation patterns and related immune microenvironment in idiopathic pulmonary arterial hypertension |
| title_short | Comprehensive analyses of m6A RNA methylation patterns and related immune microenvironment in idiopathic pulmonary arterial hypertension |
| title_sort | comprehensive analyses of m6a rna methylation patterns and related immune microenvironment in idiopathic pulmonary arterial hypertension |
| topic | idiopathic pulmonary arterial hypertension m6A methylation regulators immune microenvironment human pulmonary artery smooth muscle cells platelet-derived growth factor-BB |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1222368/full |
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