Abstract
BackgroundMicroRNAs (miRNAs) play crucial roles in regulating eukaryotic gene expression. Recent studies indicated that aberrantly expressed miRNAs are involved in the pathogenesis of ankylosing spondylitis (AS). Indeed, hsa-miR-495-3p (miR-495) has been reported as an anti-oncogene in different cancers. However, the role of miR-495 in AS is still unknown.MethodsIn this study, quantitative real-time polymerase chain reaction (PCR) was used to detect the expression of miR-495 in the peripheral blood mononuclear cells (PBMCs), whole blood, and serum of patients with AS. Bisulfite-specific PCR sequencing and methylated DNA immunoprecipitation were used to detect the methylation in the promoter region of miR-495. To determine the influence of miR-495 expression on the target gene, programmed cell death 10 (PDCD10), dual luciferase reporter assays together with an adenoviral vector containing the miR-495 locus were used. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of miR-495 as a diagnostic biomarker of AS. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and western blotting were used to explore the potential role of miR-495 in AS pathogenesis and the mechanism by which it facilitates AS pathogenesis.ResultsmiR-495 is down-regulated and the promoter region of miR-495 is highly methylated in AS. The expression of miR-495 is negatively associated with PDCD10 expression in both patients with AS and healthy controls. Further experiments showed that PDCD10 can be targeted by miR-495. The ROC curves of miR-495 suggested that it is a very specific and sensitive biomarker for AS diagnosis. Bioinformatics analysis and signal pathway studies indicated that miR-495 can down-regulate β-catenin and transforming growth factor-β1.ConclusionsOur studies indicated that down-regulation of miR-495 can be used as a potential molecular marker for the diagnosis and treatment of AS, thus providing new insights into the role of miRNAs in AS pathology.
Highlights
IntroductionMicroRNAs (miRNAs) play crucial roles in regulating eukaryotic gene expression
MicroRNAs play crucial roles in regulating eukaryotic gene expression
Previous reports show that peripheral blood mononuclear cells (PBMCs), whole blood, and serum can act as a source of miRNAs to study ankylosing spondylitis (AS) (Lai et al 2013; Li et al 2016; Mohammadi et al 2018). miR-495 is significantly (P < 0.01) down-regulated in PBMCs from patients with AS (Fig. 1a)
Summary
MicroRNAs (miRNAs) play crucial roles in regulating eukaryotic gene expression. Ankylosing spondylitis (AS) is a chronic autoimmune disease that can result in functional and structural impairments by affecting the sacroiliac joint and the axial skeleton Multilevel complex interactions between genetic, epigenetic and environmental factors play important roles during AS development (Zhu et al 2019). The onset of AS is usually early and affects more men than women (Feldtkeller et al 2003). Antiinflammatory agents, and physiotherapy approaches have been developed for diagnosing and treating AS, significant challenges still remain in the early diagnosis and treatment of AS (Braun and Sieper 2007; Danve and O'Dell 2015)
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