microRNA involvement in the regulation of survivin in peripheral blood mononuclear cells from rheumatoid arthritis patients

• Published in: International journal of rheumatic diseases Vol. 22; no. 6; pp. 1107 - 1114
• Main Authors: Ebrahimiyan, Hamidreza, Rezaei, Nima, Vojdanian, Mahdi, Aslani, Saeed, Jamshidi, Ahmadreza, Mahmoudi, Mahdi
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.06.2019
• Subjects: Adult; Apoptosis; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - genetics; Autoimmune diseases; Case-Control Studies; Complementary DNA; Female; Gene expression; Gene Expression Regulation; Humans; immune tolerance; Immunological tolerance; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Male; microRNA; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; miRNA; Mitosis; Peripheral blood mononuclear cells; Polymerase chain reaction; Rheumatoid arthritis; RNA, Messenger - blood; RNA, Messenger - genetics; Survivin; Survivin - blood; Survivin - genetics; Transcription; survivin; apoptosis; microRNA; immune tolerance; rheumatoid arthritis
• ISSN: 1756-1841; 1756-185X; 1756-185X
• DOI: 10.1111/1756-185X.13520

Aim Impaired regulation of immune tolerance results in autoimmune diseases, such as rheumatoid arthritis (RA). Survivin is an anti‐apoptotic protein and can induce cellular mitosis. In the current study, we assessed the transcript level of total survivin (survivin‐TS) and its three major variants and evaluated the expression level of important micro RNAs (miRNAs) involved in survivin expression regulation in RA patients. Method Peripheral blood mononuclear cells (PBMCs) were isolated from 50 healthy controls and 50 RA‐active patients. RNA extraction was performed and then single‐strand complementary DNA was synthesized. Quantitative real‐time polymerase chain reaction was used to assess the expression level of survivin‐TS and its variants with effective miRNAs in PBMCs. Results Overexpression of survivin‐2B (fold change = 1.57, P = 0.005), survivn‐ΔEx3 (fold change = 1.93, P = 0.009) and downregulation of survivin‐WT (fold change = 0.64, P = 0.0002) were found in PBMCs of patients, while messenger RNA (mRNA) expression of survivin‐TS had no significant difference between RA patients and controls. Expression levels of miR‐335‐5p, miR‐485‐5p, miR‐16‐5p, miR‐150‐5p, miR‐34a‐5p, and miR‐203a‐3p were significantly increased in PBMCs from patients compared with healthy controls. In a correlation study, dysregulation of these miRNAs were not correlated with mRNA expression level of survivin. Conclusion While survivin‐TS was not differently expressed in RA patients, its variants had altered expression. Although miRNAs were aberrantly expressed in PBMCs from RA subjects, they did not regulate survivin‐TS. miRNAs might be involved in RA pathogenesis, but not through controlling survivin.