MicroRNA-653 Inhibits Thymocyte Proliferation and Induces Thymocyte Apoptosis in Mice with Autoimmune Myasthenia Gravis by Downregulating TRIM9
Authors: Wei Han
Yu-Zhi Li
Wei Dong
Yu-Ling Cao
Journal: Neuroimmunomodulation (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Apoptosis; Autoimmune myasthenia gravis; MicroRNA-653; Proliferation; Thymocyte
Affiliations: Department of Neurology, Jining No. 1 People's Hospital, Jining, China., Department of Emergency, Jining No. 1 People's Hospital, Jining, China, .

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. 

Retracted: No

PubPeer comments:
 Fig 6a.  Cell cycle diagram determined by flow cytometry . Upon examining the fine detail in these flaw-cytometry plots, they do not make a lot of sense and appear to be hand-drawn. ![file] , 
 We did do the flow experiment, including the parameters set at the time and the test graphics, and the related raw data were in the flow test computer, because the graduate student in charge of this study has graduated and the laboratory equipment has been updated, so the data is not available at this time. If you feel the data is unreliable, we also agree to retract the article. , 
 We did do the flow experiment, including the parameters set at the time and the test graphics, and the related raw data were in the flow test computer, because the graduate student in charge of this study has graduated and the laboratory equipment has been updated, so the data is not available at this time. If you feel the data is unreliable, we also agree to retract the article. , 
 We did do the flow experiment, including the parameters set at the time and the test graphics, and the related raw data were in the flow test computer, because the graduate student in charge of this study has graduated and the laboratory equipment has been updated, so the data is not available at this time. If you feel the data is unreliable, we also agree to retract the article. , 
 #4 My key advice is not to listen to the advice of some anonymous commentor whose expertise and qualifications are unknown. If you suspect that my concerns about the flow-cytometry plots have any validity, you should consult an expert in the method, and -- most important -- you should consult the editor of the journal. , 
 #5 Thank you so much for your attention to our article, pointing out what we ignore, and in the next step we will discuss this issue with the editor of the magazine! In the future, we will also learn from this rigorous attitude towards science! ,