Dataset Information

Serum miR-3620-3p as a Novel Biomarker for Ankylosing Spondylitis.

ABSTRACT:

Objective

Using microRNA (miR) as a biomarker has been a new way for diagnosing many diseases Although many studies on miR-biomarker have been published, researches on miR-biomarker in ankylosing spondylitis (AS) are limited Therefore, the objective of this study was to valiate a candidate serum miR as a novel disease-specific novel miR for AS.

Methods

Total RNAs were extracted from sera samples of patients with AS (n=57), patients with rheumatoid arthritis (RA) (n=37), or healthy controls (HC) (n=19) Through serum miR screening by microarray, differential levels of miR were subsequently validated by real time PCR At the time of serum sampling, clinical values such as sex, age, disease duration, AS-disease activity score, uveitis, peripheral arthritis, enthesitis, human leukocyte antigen-B27 presence, and recent medication were evaluated.

Results

We found that the expression level of serum miR-3620-3p in AS was notably lower than that in RA or HC The receiver-operator characteristics curve for determining the diagnostic accuracy showed an area under the curve of 0919 (p<0001) with a sensitivity of 871% and a specificity of 860% Correlation studies showed that the expression level of miR-3620-3p was only associated with the development of uveitis (p<005).

Conclusion

Serum miR-3620-3p can be as a new biomarker for diagnosing AS.

SUBMITTER: Lee HI

PROVIDER: S-EPMC10324918 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Serum miR-3620-3p as a Novel Biomarker for Ankylosing Spondylitis.

Lee Hae-In HI Park Ki-Jeong KJ Kim Hui-Ju HJ Choi Ah-Ra AR Jin So-Hee SH Kim Tae-Jong TJ

Journal of rheumatic diseases 20220101 1

<h4>Objective</h4>Using microRNA (miR) as a biomarker has been a new way for diagnosing many diseases Although many studies on miR-biomarker have been published, researches on miR-biomarker in ankylosing spondylitis (AS) are limited Therefore, the objective of this study was to valiate a candidate serum miR as a novel disease-specific novel miR for AS.<h4>Methods</h4>Total RNAs were extracted from sera samples of patients with AS (n=57), patients with rheumatoid arthritis (RA) (n=37), or healthy ...[more]

PMID: 37476698

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Project description:Ankylosing spondylitis (AS) is a chronic autoimmune disease in which let-7i has been studied to involved. But, whether let-7i-3p could regulate osteoblast differentiation in AS remains unclear. This research targeted to decipher the impact of let-7i-3p on AS progression by modulating pyruvate dehydrogenase kinase 1 (PDK1). The bone mineral density of femur and lumbar vertebra and the maximum loading and bending elastic modulus of tibia, tumor necrosis factor-α (TNF-α), matrix metalloproteinase (MMP)-3, osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in serum of AS mice, the pathological condition of synovial tissue were determined via let-7i-3p inhibitor and OE-PDK1 in animal experiment. Also, the cell viability and ALP activity were measured by let-7i-3p inhibitor and OE-PDK1 in cell experiments. let-7i-3p and PDK1 expression were detected. Let-7i-3p raised and PDK1 declined in AS mice. Depleted let-7i-3p and restored PDK1 increased bone mineral density and maximum loading and bending elastic modulus of tibia, reduced TNF-α, MMP-3 and RANKL contents, attenuated the pathological condition of synovial tissue and raised OPG content in AS mice. In cell experiments, up-regulating PDK1 and down-regulating let-7i-3p enhanced cell viability and ALP activity in AS mice. Low expression of let-7i-3p could enhance osteoblast differentiation in AS by up-regulating PDK1.Abbreviations: AS: Ankylosing spondylitis; PDK1: pyruvate dehydrogenase kinase 1; TNF-α: tumor necrosis factor-α MMP: matrix metalloproteinase; OPG: osteoprotegerin; RANKL: receptor activator of nuclear factor-κB ligand; miRNAs: MicroRNAs; BMD: bone mineral density; PFA: paraformaldehyde; NC: negative control; OE: overexpression; HE: Hematoxylin-eosin; PBS: phosphate-buffered saline; EDTA: ethylene diamine tetraacetic acid; DMEM: Dulbecco's Modified Eagle Medium; RT-qPCR: Reverse transcription quantitative polymerase chain reaction; GAPDH: glyceraldehyde phosphate dehydrogenase; UTR: untranslated region; WT: wild type; MUT: mutant type.

Project description:BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory arthritis. Upregulation of microRNA (miR)-92b-3p is associated with enhanced osteoblastic differentiation. The current study sought to investigate the functional mechanism of miR-92b-3p in osteogenic differentiation of AS fibroblasts.MethodsFirst, fibroblasts were isolated from AS and non-AS patients and cultured. Next, cell morphology was observed, cell proliferation was assessed and the vimentin expression pattern was determined. Alkaline phosphatase (ALP) activity and levels of osteogenic markers RUNX2, OPN, OSX, and COL I were additionally measured, followed by determination of miR-92b-3p and TOB1 levels. The binding site of miR-92b-3p and TOB1 was predicted, and their target relationship was validated. Lastly, miR-92b-3p inhibitor, si-TOB1, and the BMP/Smad signaling pathway inhibitor LDN193189 were delivered into AS fibroblasts to evaluate the osteogenic differentiation of AS fibroblasts and the activation of the BMP/Smad pathway.ResultsmiR-92b-3p was highly expressed in AS fibroblasts. AS fibroblasts showed enhanced osteogenic differentiation and proliferation, while inhibition of miR-92b-3p suppressed osteogenic differentiation and proliferation of AS fibroblasts. miR-92b-3p targeted TOB1, and TOB1 was poorly expressed in AS fibroblasts. The concurrent downregulation of TOB1 and inhibition of miR-92b-3p elevated the levels of RUNX2, OPN, OSX, and COL I and ALP activity and further enhanced the proliferation of AS fibroblasts. The BMP/Smad pathway was activated in AS fibroblasts. Silencing miR-92b-3p could inhibit the activation of the BMP/Smad pathway by upregulating TOB1. Inhibition of the BMP/Smad pathway reduced the number of calcified nodules and hindered the osteogenic differentiation and proliferation of AS fibroblasts.ConclusionOur findings highlighted that silencing miR-92b-3p inhibited the osteogenic differentiation and proliferation of AS fibroblasts by upregulation of TOB1 and inhibition of the BMP/Smad pathway.

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Dataset Information

Serum miR-3620-3p as a Novel Biomarker for Ankylosing Spondylitis.

Objective

Methods

Results

Conclusion

Publications

Serum miR-3620-3p as a Novel Biomarker for Ankylosing Spondylitis.

Similar Datasets

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