The potential role of RNA N6-methyladenosine in primary Sjögren’s syndrome
ObjectiveThe pathogenesis of primary Sjögren’s syndrome (pSS) remains incompletely understood. The N6-methyladenosine (m6A) RNA modification, the most abundant internal transcript modification, has close associations with multiple diseases. This study aimed to investigate the role of m6A in patients...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.959388/full |
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| author | Qiufeng Xiao Qiufeng Xiao Qiufeng Xiao Qiufeng Xiao Xunyao Wu Chuiwen Deng Chuiwen Deng Chuiwen Deng Chuiwen Deng Lidan Zhao Lidan Zhao Lidan Zhao Lidan Zhao Linyi Peng Linyi Peng Linyi Peng Linyi Peng Jiaxin Zhou Jiaxin Zhou Jiaxin Zhou Jiaxin Zhou Wen Zhang Wen Zhang Wen Zhang Wen Zhang Yan Zhao Yan Zhao Yan Zhao Yan Zhao Yunyun Fei Yunyun Fei Yunyun Fei Yunyun Fei |
| author_facet | Qiufeng Xiao Qiufeng Xiao Qiufeng Xiao Qiufeng Xiao Xunyao Wu Chuiwen Deng Chuiwen Deng Chuiwen Deng Chuiwen Deng Lidan Zhao Lidan Zhao Lidan Zhao Lidan Zhao Linyi Peng Linyi Peng Linyi Peng Linyi Peng Jiaxin Zhou Jiaxin Zhou Jiaxin Zhou Jiaxin Zhou Wen Zhang Wen Zhang Wen Zhang Wen Zhang Yan Zhao Yan Zhao Yan Zhao Yan Zhao Yunyun Fei Yunyun Fei Yunyun Fei Yunyun Fei |
| author_sort | Qiufeng Xiao |
| collection | DOAJ |
| description | ObjectiveThe pathogenesis of primary Sjögren’s syndrome (pSS) remains incompletely understood. The N6-methyladenosine (m6A) RNA modification, the most abundant internal transcript modification, has close associations with multiple diseases. This study aimed to investigate the role of m6A in patients with pSS.Materials and methodsThis study enrolled 44 patients with pSS, 50 age- and gender-matched healthy controls (HCs), and 11 age- and gender-matched patients with non-SS sicca. We detected the messenger RNA (mRNA) levels of m6A elements (including METTL3, WTAP, RBM15, ALKBH5, FTO, YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2), ISG15, and USP18 in peripheral blood mononuclear cells (PBMCs) from patients with pSS, patients with non-SS sicca, and HCs. The clinical characteristics and laboratory findings of patients with pSS and patients with non-SS sicca were also collected. We used binary logistic regression to determine if m6A elements were risk factors for pSS.ResultsThe mRNA levels of m6A writers (METTL3 and RBM15), erasers (ALKBH5 and FTO), and readers (YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2) were all significantly higher in PBMCs from patients with pSS than in HCs. The mRNA levels of m6A writers (METTL3 and WTAP) and readers (YTHDF2, YTHDF3, and YTHDC2) were lower in PBMCs from patients with pSS compared to patients with non-SS sicca. The expression of METTL3, RBM15, FTO, YTHDF1, YTHDF2, YTHDC1, and YTHDC2 was positively correlated with the level of C-reactive protein (CRP) of patients with pSS. The mRNA level of YTHDF1 in PBMCs from patients with pSS was negatively correlated with the EULAR Sjögren’s syndrome disease activity index (ESSDAI) score. In patients with pSS, FTO, YTHDC1, and YTHDC2 were also related to white blood cells (WBCs), neutrophils, lymphocytes, and monocytes. Increased mRNA level of ALKBH5 in PBMCs was a risk factor for pSS, as determined by binary logistic regression analysis. The mRNA level of ISG15 was positively correlated with that of FTO, YTHDF2, YTHDF3, and YTHDC2 in patients with pSS.ConclusionCompared with HCs, the expression of METTL3, RBM15, ALKBH5, FTO, YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2 was considerably higher in PBMCs from patients with pSS. In comparison with patients with non-SS sicca, the expression of METTL3, WTAP, YTHDF2, YTHDF3, and YTHDC2 was reduced in PBMCs from patients with pSS. The m6A elements correlating with clinical variables may indicate the disease activity and inflammation status of pSS. Elevated expression of ALKBH5 was a risk factor for pSS. The dynamic process of m6A modification is active in pSS. m6A elements (FTO, YTHDF2, YTHDF3, or YTHDC2) might target ISG15, stimulate the expression of ISG15, and activate the type I IFN signaling pathway, playing an active role in initiating the autoimmunity in pSS. |
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| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-03-13T00:17:25Z |
| publishDate | 2022-11-01 |
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| spelling | doaj.art-71dc567929b644c886f22f9a572fee422023-07-11T19:09:05ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-11-01910.3389/fmed.2022.959388959388The potential role of RNA N6-methyladenosine in primary Sjögren’s syndromeQiufeng Xiao0Qiufeng Xiao1Qiufeng Xiao2Qiufeng Xiao3Xunyao Wu4Chuiwen Deng5Chuiwen Deng6Chuiwen Deng7Chuiwen Deng8Lidan Zhao9Lidan Zhao10Lidan Zhao11Lidan Zhao12Linyi Peng13Linyi Peng14Linyi Peng15Linyi Peng16Jiaxin Zhou17Jiaxin Zhou18Jiaxin Zhou19Jiaxin Zhou20Wen Zhang21Wen Zhang22Wen Zhang23Wen Zhang24Yan Zhao25Yan Zhao26Yan Zhao27Yan Zhao28Yunyun Fei29Yunyun Fei30Yunyun Fei31Yunyun Fei32Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaNational Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science and Technology, Beijing, ChinaState Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, ChinaClinical Biobank, Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaNational Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science and Technology, Beijing, ChinaState Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, ChinaDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaNational Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science and Technology, Beijing, ChinaState Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, ChinaDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaNational Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science and Technology, Beijing, ChinaState Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, ChinaDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaNational Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science and Technology, Beijing, ChinaState Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, ChinaDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaNational Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science and Technology, Beijing, ChinaState Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, ChinaDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaNational Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science and Technology, Beijing, ChinaState Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, ChinaDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaNational Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science and Technology, Beijing, ChinaState Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, ChinaObjectiveThe pathogenesis of primary Sjögren’s syndrome (pSS) remains incompletely understood. The N6-methyladenosine (m6A) RNA modification, the most abundant internal transcript modification, has close associations with multiple diseases. This study aimed to investigate the role of m6A in patients with pSS.Materials and methodsThis study enrolled 44 patients with pSS, 50 age- and gender-matched healthy controls (HCs), and 11 age- and gender-matched patients with non-SS sicca. We detected the messenger RNA (mRNA) levels of m6A elements (including METTL3, WTAP, RBM15, ALKBH5, FTO, YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2), ISG15, and USP18 in peripheral blood mononuclear cells (PBMCs) from patients with pSS, patients with non-SS sicca, and HCs. The clinical characteristics and laboratory findings of patients with pSS and patients with non-SS sicca were also collected. We used binary logistic regression to determine if m6A elements were risk factors for pSS.ResultsThe mRNA levels of m6A writers (METTL3 and RBM15), erasers (ALKBH5 and FTO), and readers (YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2) were all significantly higher in PBMCs from patients with pSS than in HCs. The mRNA levels of m6A writers (METTL3 and WTAP) and readers (YTHDF2, YTHDF3, and YTHDC2) were lower in PBMCs from patients with pSS compared to patients with non-SS sicca. The expression of METTL3, RBM15, FTO, YTHDF1, YTHDF2, YTHDC1, and YTHDC2 was positively correlated with the level of C-reactive protein (CRP) of patients with pSS. The mRNA level of YTHDF1 in PBMCs from patients with pSS was negatively correlated with the EULAR Sjögren’s syndrome disease activity index (ESSDAI) score. In patients with pSS, FTO, YTHDC1, and YTHDC2 were also related to white blood cells (WBCs), neutrophils, lymphocytes, and monocytes. Increased mRNA level of ALKBH5 in PBMCs was a risk factor for pSS, as determined by binary logistic regression analysis. The mRNA level of ISG15 was positively correlated with that of FTO, YTHDF2, YTHDF3, and YTHDC2 in patients with pSS.ConclusionCompared with HCs, the expression of METTL3, RBM15, ALKBH5, FTO, YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2 was considerably higher in PBMCs from patients with pSS. In comparison with patients with non-SS sicca, the expression of METTL3, WTAP, YTHDF2, YTHDF3, and YTHDC2 was reduced in PBMCs from patients with pSS. The m6A elements correlating with clinical variables may indicate the disease activity and inflammation status of pSS. Elevated expression of ALKBH5 was a risk factor for pSS. The dynamic process of m6A modification is active in pSS. m6A elements (FTO, YTHDF2, YTHDF3, or YTHDC2) might target ISG15, stimulate the expression of ISG15, and activate the type I IFN signaling pathway, playing an active role in initiating the autoimmunity in pSS.https://www.frontiersin.org/articles/10.3389/fmed.2022.959388/fullprimary Sjögren’s syndromeN6-methyladenosineMETTL3ALKBH5YTHDF readersISG15 |
| spellingShingle | Qiufeng Xiao Qiufeng Xiao Qiufeng Xiao Qiufeng Xiao Xunyao Wu Chuiwen Deng Chuiwen Deng Chuiwen Deng Chuiwen Deng Lidan Zhao Lidan Zhao Lidan Zhao Lidan Zhao Linyi Peng Linyi Peng Linyi Peng Linyi Peng Jiaxin Zhou Jiaxin Zhou Jiaxin Zhou Jiaxin Zhou Wen Zhang Wen Zhang Wen Zhang Wen Zhang Yan Zhao Yan Zhao Yan Zhao Yan Zhao Yunyun Fei Yunyun Fei Yunyun Fei Yunyun Fei The potential role of RNA N6-methyladenosine in primary Sjögren’s syndrome Frontiers in Medicine primary Sjögren’s syndrome N6-methyladenosine METTL3 ALKBH5 YTHDF readers ISG15 |
| title | The potential role of RNA N6-methyladenosine in primary Sjögren’s syndrome |
| title_full | The potential role of RNA N6-methyladenosine in primary Sjögren’s syndrome |
| title_fullStr | The potential role of RNA N6-methyladenosine in primary Sjögren’s syndrome |
| title_full_unstemmed | The potential role of RNA N6-methyladenosine in primary Sjögren’s syndrome |
| title_short | The potential role of RNA N6-methyladenosine in primary Sjögren’s syndrome |
| title_sort | potential role of rna n6 methyladenosine in primary sjogren s syndrome |
| topic | primary Sjögren’s syndrome N6-methyladenosine METTL3 ALKBH5 YTHDF readers ISG15 |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.959388/full |
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