Characterization of antiapoptotic microRNAs in primary Sjögren's syndrome. (23rd June 2020)

• Record Type: Journal Article
• Authors: Yang, Ying; Hou, Yingzi; Li, Jinghui; Zhang, Fangming; Du, Quan
• Is Part Of: Cell biochemistry and function. Volume 38:Number 8(2020)
• Page Start: 1111
• Page End: 1118
• Publication Date: 2020-06-23
• Subjects: caspase 8 -- cell apoptosis -- miR‐1207‐5p -- miR‐4695‐3p -- primary Sjögren's syndrome (pSS); Cytochemistry -- Periodicals; Cell metabolism -- Periodicals; Biochemistry -- Periodicals; Cytology -- Periodicals; 572
• DOI: 10.1002/cbf.3569
• Languages: English
• ISSNs: 0263-6484

Abstract

Abstract : During the development of primary Sjögren's syndrome (pSS), aberrant expression of autoantigen is a hallmark event. To explore the regulation of autoantigen tripartite motif containing 21 (Ro/SSA, TRIM21), microRNA profiling was performed in our previous study. In which, two TRIM21 ‐targeting microRNAs were identified, namely miR‐1207‐5p and miR‐4695‐3p. To further pursue their roles in the development of pSS, assays were performed with cultured human submandibular gland (HSG) cells, and salivary gland tissues. Results showed that transfection of miR‐1207‐5p or miR‐4695‐3p mimics down‐regulated not only the expression of TRIM21, but also the levels of pro‐apoptotic genes B cell lymphoma 2 associated X ( BAX ), Caspase 9 ( CASP‐9 ) and Caspase 8 ( CASP‐8 ). This finally led to antiapoptotic phenotypes in HSG cells. Consistent with the antiapoptotic activity, transfection of microRNA inhibitors up‐regulated the expression of TRIM21 and led to a pro‐apoptotic phenotype. These therefore propose miR‐1207‐5p and miR‐4695‐3p as two antiapoptotic microRNAs functioning through apoptosis pathway. Supporting this speculation, assays performed with salivary gland tissues revealed down‐regulation of miR‐1207‐5p and miR‐4695‐3p, as well as up‐regulation of TRIM21 and pro‐apoptotic CASP‐8 gene in pSS samples. Significance of the study: For pSS patients, apoptosis of acinar and ductal epithelial cells has been proposed to be a potential mechanism that impairs the secretion of salivary glands. In our study, two autoantigen‐targeting microRNAs were characterized as antiapoptotic microRNAs functioning through apoptosis pathway, which may be potential targets for the treatment of pSS.