{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:17:02Z","timestamp":1791919022435,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,1,22]],"date-time":"2022-01-22T00:00:00Z","timestamp":1642809600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["15JJ3132"],"award-info":[{"award-number":["15JJ3132"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["81502359"],"award-info":[{"award-number":["81502359"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["15JJ3132"],"award-info":[{"award-number":["15JJ3132"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81502359"],"award-info":[{"award-number":["81502359"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2022,1,22]]},"abstract":"<jats:p>Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease that is characterized by autoimmunity and its mediated \u03b2-cell damage. Chronic exposure of \u03b2-cells to proinflammatory cytokines is known to regulate the expression of many genes, subsequently resulting in the impairment of some signaling pathways involved with insulin production and secretion and\/or \u03b2-cell apoptosis. In our study, RNA sequencing technology was applied to identify differentially expressed mRNAs in MIN6 cells treated with a mix of cytokines, including IL-1\u03b2, TNF-\u03b1, and IFN-\u03b3. The results showed 809 upregulated and 946 downregulated protein-coding mRNAs in MIN6 cells upon the stimulation of cytokines. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses were performed to predict the functions of dysregulated genes. The networks of circRNA-mRNA were constructed between differentially mRNAs and dysregulated expressed circRNAs in our previous study. In addition, we selected 8 dysregulated mRNAs for further validation by quantitative real-time PCR. The RNA sequencing data showed 809 upregulated and 946 downregulated protein-coding mRNAs. GO analysis showed that the top 10 significant \u201cbiological processes,\u201d \u201ccellular components,\u201d and \u201cmolecular functions\u201d for upregulated mRNAs include \u201cimmune system process,\u201d \u201cinflammatory response,\u201d and \u201cinnate immune response\u201d and the top 10 for downregulated mRNAs include \u201ccell cycle,\u201d \u201cmitotic cytokinesis,\u201d and \u201ccytoplasm.\u201d KEGG analysis showed that these differentially expressed genes were involved with \u201cantigen processing and presentation,\u201d \u201cTNF signaling pathway\u201d and \u201ctype 1 diabetes,\u201d \u201ccell cycle,\u201d \u201cnecroptosis,\u201d and \u201cRap1 signaling pathway.\u201d We also constructed the networks of differentially expressed circRNAs and mRNAs. We observed that upregulated circRNA 006029 and downregulated circRNA 000286 and 017277 were associated with the vast majority of selected dysregulated mRNAs, while circRNA 013053 was only related to the protein-coding gene, Slc7a2. To the summary, these data indicated that differentially expressed mRNAs may play key or partial roles in cytokine-mediated \u03b2-cell dysfunction and gave us the hint that circRNAs might regulate mRNAs, thereby contributing to the development of T1DM. The current study provided a systematic perspective on the potential functions and possible regulatory mechanisms of mRNAs in proinflammatory cytokine-induced \u03b2-cell destruction.<\/jats:p>","DOI":"10.1155\/2022\/4542487","type":"journal-article","created":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T04:35:10Z","timestamp":1642912510000},"page":"1-9","source":"Crossref","is-referenced-by-count":5,"title":["Insights from Dysregulated mRNA Expression Profile of \u03b2-Cells in Response to Proinflammatory Cytokines"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6401-4968","authenticated-orcid":true,"given":"Zhen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China"},{"name":"Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, Changsha, Hunan 410011, China"},{"name":"National Clinical Research Center for Metabolic Diseases, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8827-5348","authenticated-orcid":true,"given":"Kunlin","family":"Huang","sequence":"additional","affiliation":[{"name":"Center for Medical Research, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5080-9279","authenticated-orcid":true,"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, The First People\u2019s Hospital of Pingjiang, Pingjiang, Hunan 414500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9319-5841","authenticated-orcid":true,"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Medical Research, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5084-0142","authenticated-orcid":true,"given":"Ying","family":"Zheng","sequence":"additional","affiliation":[{"name":"Center for Medical Research, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"issue":"4","key":"1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrendo.2009.21","article-title":"The role of inflammation in insulitis and beta-cell loss in type 1 diabetes","volume":"5","author":"D. 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