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Characterization of antiapoptotic microRNAs in primary Sjögren's syndrome.
CELL BIOCHEMISTRY AND FUNCTION ( IF 3.6 ) Pub Date : 2020-06-23 , DOI: 10.1002/cbf.3569
Ying Yang 1 , Yingzi Hou 2 , Jinghui Li 1 , Fangming Zhang 1 , Quan Du 2
Affiliation  

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.

中文翻译:

原发性干燥综合征中抗凋亡microRNA的表征。

在原发性干燥综合征(pSS)的发展过程中,自身抗原的异常表达是一个标志性事件。为了探索包含21(Ro / SSA,TRIM21)的自身抗原三方基序的调控,在我们之前的研究中进行了microRNA分析。其中鉴定了两个靶向TRIM21的microRNA,即miR-1207-5p和miR-4695-3p。为了进一步追求其在pSS发育中的作用,对培养的人类下颌下腺(HSG)细胞和唾液腺组织进行了测定。结果表明,miR-1207-5p或miR-4695-3p的转染不仅下调了TRIM21的表达,还下调了促凋亡基因B细胞淋巴瘤2相关的X(BAX),胱天蛋白酶9(CASP ‐9)和半胱天冬酶8(CASP-8)。最终导致HSG细胞中的抗凋亡表型。与抗凋亡活性一致,microRNA抑制剂的转染上调了TRIM21的表达并导致了促凋亡表型。因此,这些建议将miR-1207-5p和miR-4695-3p作为通过细胞凋亡途径起作用的两个抗凋亡microRNA。支持这一推测的唾液腺组织检测显示,pSS样品中miR-1207-5p和miR-4695-3p的表达下调,而TRIM21和促凋亡的CASP-8基因的表达也上调。
更新日期:2020-06-23
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