Journal
TRANSPLANT IMMUNOLOGY
Volume 75, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.trim.2022.101685
Keywords
Rheumatoid arthritis; circPTTG1IP; miR-431-5p; FSTL1
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The study suggests that circPTTG1IP plays a key role in the pathology of RA and suppresses the progression of RA through regulating the miR-431-5p/FSTL1 signaling cascade.
Background: It is observed that circular RNA (circRNA) PTTG1 interacting protein (circPTTG1IP) level is notably up-regulated in rheumatoid arthritis (RA) patients by previous study. However, its precise role and working mechanism in RA pathology remain to be clarified. Methods and results: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were carried out to examine RNA and protein expression. Cell proliferation was analyzed by colony formation assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay. Cell motility was assessed by transwell assays and wound healing assay. Flow cytometry (FCM) analysis was performed to assess cell apoptosis rate. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA-pull down assays were conducted to confirm the interaction between microRNA-431-5p (miR-431-5p) and circPTTG1IP or follistatin like 1 (FSTL1). CircPTTG1IP expression was up-regulated in the synovial tissues of RA patients and RA patients-derived fibroblast-like synoviocytes (RA-FLS). CircPTTG1IP absence suppressed the proliferation, migration, and invasion and induced the apoptosis of RA-FLS. CircPTTG1IP negatively regulated the expression of miR-431-5p by directly binding to it in RA-FLS. CircPTTG1IP interference-mediated effects in RA-FLS were largely counteracted by the silence of miR-431-5p. miR-431-5p directly interacted with the 3 & PRIME; untranslated region (3'UTR) of FSTL1. FSTL1 overexpression largely overturned miR-431-5p accumulation-mediated effects in RA-FLS. CircPTTG1IP positively regulated FSTL1 expression by sponging miR-431-5p in RA-FLS. Conclusion: CircPTTG1IP absence suppressed RA progression through mediating miR-431-5p/FSTL1 signaling cascade.
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