PMID- 29191214 OWN - NLM STAT- MEDLINE DCOM- 20180731 LR - 20181113 IS - 1478-6362 (Electronic) IS - 1478-6354 (Print) IS - 1478-6354 (Linking) VI - 19 IP - 1 DP - 2017 Dec 1 TI - The role of aberrant expression of T cell miRNAs affected by TNF-alpha in the immunopathogenesis of rheumatoid arthritis. PG - 261 LID - 10.1186/s13075-017-1465-z [doi] LID - 261 AB - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) can cause diverse T cell dysfunctions in patients with rheumatoid arthritis (RA). It is involved in the regulation of microRNAs (miRNAs) expression in different cell types. We hypothesized that the expression of T cell miRNAs would be affected by TNF-alpha, and these miRNAs could participate in the immunopathogenesis of RA. METHODS: Expression profiles of 270 human miRNAs in Jurkat cells, cultured in the presence or absence of TNF-alpha for 7 days were analyzed by real-time polymerase chain reaction. Potentially aberrantly expressed miRNAs were validated using T cell samples from 35 patients with RA and 15 controls. Transfection studies were conducted to search for gene expression and biological functions regulated by specific miRNAs. RESULTS: Initial analysis revealed 12 miRNAs were significantly lower, whereas the expression level of miR-146a was significantly higher in Jurkat cells after being cultured with TNF-alpha for 7 days. Decreased expression of miR-139-3p, miR-204, miR-760, miR-524-5p, miR-136, miR-548d-3p, miR-214, miR-383, and miR-887 were noted in RA T cells. Expression levels of miR-139-3p, miR-204, miR-214, and miR-760 were correlated with the use of biologic agents. The transfection of miR-214 mimic suppressed TNF-alpha-mediated apoptosis of Jurkat cells. Increased phosphorylation of extracellular regulating kinase (ERK) and c-Jun N-terminal kinase (JNK) was noted in RA T cells and Jurkat cells after TNF-alpha exposure. Transfection of Jurkat cells with miR-214 mimic suppressed both the basal and TNF-alpha-mediated ERK and JNK phosphoryation. CONCLUSIONS: Among T cell miRNAs affected by TNF-alpha, the expression levels of nine miRNAs were decreased in T cells from patients with RA. The expression levels of miR-139-3p, miR-204, miR-214, and miR-760 increased in RA patients receiving biologic agents. The transfection of miR-214 reversed the TNF-alpha-mediated cells apoptosis and inhibited the phosphorylation of ERK and JNK in Jurkat cells. FAU - Lai, Ning-Sheng AU - Lai NS AD - Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Road, Dalin, Chiayi, 62247, Taiwan. AD - School of Medicine, Tzu Chi University, Hualien City, Taiwan. FAU - Yu, Hui-Chun AU - Yu HC AD - Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Road, Dalin, Chiayi, 62247, Taiwan. FAU - Tung, Chien-Hsueh AU - Tung CH AD - Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Road, Dalin, Chiayi, 62247, Taiwan. FAU - Huang, Kuang-Yung AU - Huang KY AD - Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Road, Dalin, Chiayi, 62247, Taiwan. AD - School of Medicine, Tzu Chi University, Hualien City, Taiwan. FAU - Huang, Hsien-Bin AU - Huang HB AD - Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Minxiong, Chiayi, Taiwan. FAU - Lu, Ming-Chi AU - Lu MC AUID- ORCID: 0000-0001-9051-0351 AD - Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Road, Dalin, Chiayi, 62247, Taiwan. e360187@yahoo.com.tw. AD - School of Medicine, Tzu Chi University, Hualien City, Taiwan. e360187@yahoo.com.tw. LA - eng GR - MOST 104-2314-B-303-008-MY2/Ministry of Science and Technology, Taiwan/ PT - Journal Article DEP - 20171201 PL - England TA - Arthritis Res Ther JT - Arthritis research & therapy JID - 101154438 RN - 0 (MicroRNAs) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Apoptosis/immunology MH - Arthritis, Rheumatoid/*immunology MH - Gene Expression Regulation/*immunology MH - Humans MH - Jurkat Cells MH - MicroRNAs/*immunology MH - T-Lymphocytes/*immunology MH - Tumor Necrosis Factor-alpha/*immunology PMC - PMC5709919 OTO - NOTNLM OT - Apoptosis OT - ERK OT - JNK OT - Rheumatoid arthritis OT - T cells OT - TNF-alpha OT - microRNAs COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study was conducted in accordance with the Declaration of Helsinki and was approved by the institutional review board of Buddhist Dalin Tzu Chi Hospital, Taiwan (No. B10503007). Signed informed consent was obtained from all patients. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. EDAT- 2017/12/02 06:00 MHDA- 2018/08/01 06:00 PMCR- 2017/12/01 CRDT- 2017/12/02 06:00 PHST- 2017/06/28 00:00 [received] PHST- 2017/11/06 00:00 [accepted] PHST- 2017/12/02 06:00 [entrez] PHST- 2017/12/02 06:00 [pubmed] PHST- 2018/08/01 06:00 [medline] PHST- 2017/12/01 00:00 [pmc-release] AID - 10.1186/s13075-017-1465-z [pii] AID - 1465 [pii] AID - 10.1186/s13075-017-1465-z [doi] PST - epublish SO - Arthritis Res Ther. 2017 Dec 1;19(1):261. doi: 10.1186/s13075-017-1465-z.