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

Abstract

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.

RETRACTED: Dysregulation of Survivin-Targeting microRNAs in Autoimmune Diseases: New Perspectives for Novel Therapies

“…The implication of survivin in RA pathogenesis has been established. It is substantiated by the upregulation of survivin in serum ( 77 ), synovial fluid ( 50 ), and peripheral blood mononuclear cells (PBMCs) ( 7 ) of RA patients, underpinning its potential relevance as a diagnostic biomarker and prognostic indicator in these patients ( 78 , 79 ). It is evidenced further by research that found elevated survivin expression in patients with juvenile idiopathic arthritis to contribute to polyarticular involvement and systemic disease progression ( 80 ).…”

“…Upregulated survivin expression in autoreactive immune cells from patients with various autoimmune diseases has been evidenced in this context. Further investigation into the regulatory pathways of survivin mRNA in these cells has shown the emerging role of survivin-targeting miRNAs in the maintenance of autoreactivity ( 7 , 8 ).…”

Identification of key genes in non-small cell lung cancer by bioinformatics analysis

“…BIRC5 is a new member of the apoptosis inhibitory protein family and is the most potent inhibitor of apoptosis. BIRC5 has complex biological functions, inhibits apoptosis, promotes cell transformation and participates in cell mitosis, angiogenesis and drug resistance (Ebrahimiyan et al., 2019). It was reported that the expression level of BIRC5 was significantly higher in NSCLC tissues compared to non-tumor tissues, and negatively correlated with Tp53 (Wang et al., 2018; Vayshlya et al., 2008).…”

Identification of diagnostic genes and vital microRNAs involved in rheumatoid arthritis: based on data mining and experimental verification

“…However, some scholars hold the opposite view. It has been shown that miR-34a expression was up-regulated in PBMCs from RA patients ( Ebrahimiyan et al, 2019 ; Xie et al, 2019 ), and silencing miR-34a markedly reduced release of inflammatory mediators ( Kurowska-Stolarska et al, 2017 ). In other autoimmune diseases, such as Sjögren Syndrome, the level of miR-34a was also significantly elevated in patients ( Kim et al, 2019 ).…”