Yu-Ling Cao1, Wei Dong2, Yu-Zhi Li1, Wei Han1. 1. Department of Neurology, Jining No. 1 People's Hospital, Jining, China. 2. Department of Emergency, Jining No. 1 People's Hospital, Jining, China, dongwei_jn@126.com.
Abstract
OBJECTIVES: Myasthenia gravis (MG) is an organ-specific autoimmune neuromuscular disorder that occurs as a result of the impairment in neuromuscular junction and autoantibody attack on the postsynaptic receptors. Increasing evidence suggests that microRNAs (miRs) might be involved in the development of MG. Therefore, the present study aimed to investigate the regulatory function of miR-653 on MG and its relationship with tripartite motif 9 (TRIM9). METHODS: The thymic tissues obtained from MG patients with thymic hyperplasia were prepared for establishing an MG mouse model in BALB/c mice. Afterwards, the miR-653 and TRIM9 expressions were determined in thymic tissues. A dual-luciferase reporter assay was carried out to validate whether miR-653 directly targets TRIM9. Finally, the thymocytes were exposed to mimics or inhibitors of miR-653, or siRNA against TRIM9 with the use of MTT assays and flow cytometry for the verification of the gain or loss function of miR-653 and TRIM9 on viability, cell cycle progression, and apoptosis of thymocytes. RESULTS: There was a decrease in thymocyte miR-653 and an increase in TRIM9 in thymic tissues of MG mice. miR-653 was found to negatively regulate TRIM9. Overexpression of miR-653 or depletion of TRIM9 resulted in the inhibition of cell viability, suppression of cell cycle progression, and induction of apoptosis rate in thymocytes. CONCLUSION: The findings from the present study provided evidence that miR-653 impairs proliferation and promotes apoptosis of thymocytes of MG mice by suppressing TRIM9, indicating that miR-653 could be used as potential therapeutic target in the treatment of autoimmune MG.
OBJECTIVES:Myasthenia gravis (MG) is an organ-specific autoimmune neuromuscular disorder that occurs as a result of the impairment in neuromuscular junction and autoantibody attack on the postsynaptic receptors. Increasing evidence suggests that microRNAs (miRs) might be involved in the development of MG. Therefore, the present study aimed to investigate the regulatory function of miR-653 on MG and its relationship with tripartite motif 9 (TRIM9). METHODS: The thymic tissues obtained from MG patients with thymic hyperplasia were prepared for establishing an MG mouse model in BALB/c mice. Afterwards, the miR-653 and TRIM9 expressions were determined in thymic tissues. A dual-luciferase reporter assay was carried out to validate whether miR-653 directly targets TRIM9. Finally, the thymocytes were exposed to mimics or inhibitors of miR-653, or siRNA against TRIM9 with the use of MTT assays and flow cytometry for the verification of the gain or loss function of miR-653 and TRIM9 on viability, cell cycle progression, and apoptosis of thymocytes. RESULTS: There was a decrease in thymocyte miR-653 and an increase in TRIM9 in thymic tissues of MG mice. miR-653 was found to negatively regulate TRIM9. Overexpression of miR-653 or depletion of TRIM9 resulted in the inhibition of cell viability, suppression of cell cycle progression, and induction of apoptosis rate in thymocytes. CONCLUSION: The findings from the present study provided evidence that miR-653 impairs proliferation and promotes apoptosis of thymocytes of MG mice by suppressing TRIM9, indicating that miR-653 could be used as potential therapeutic target in the treatment of autoimmune MG.
Authors: Mohammad Taheri; Dominik A Barth; Julia Kargl; Omidvar Rezaei; Soudeh Ghafouri-Fard; Martin Pichler Journal: Front Immunol Date: 2021-11-04 Impact factor: 7.561