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Small RNA-seq analysis of serum miRNAs from patients with systemic sclerosis, Raynaud’s phenomenon, and healthy controls

ABSTRACT: Systemic sclerosis (SSc) is a complex autoimmune disease characterized by microvascular dysfunction, immune dysregulation, and progressive fibrosis, and can be classified into limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) forms. Primary Raynaud’s phenomenon (RP) is a functional vascular disorder that may precede or occur independently of connective tissue diseases. Circulating microRNAs (miRNAs) have emerged as regulators of vascular and immune processes and can be detected in serum. In this study, serum miRNA profiles were assessed in patients with SSc, including lcSSc and dcSSc subtypes, RP, and healthy controls. Small RNA sequencing was performed in a discovery cohort to characterize circulating miRNA expression across the study groups. Libraries were prepared from serum-derived RNA and sequenced on an Illumina platform. Raw sequencing data were processed using a standardized pipeline for miRNA quantification, and normalized counts were generated for downstream analyses. This dataset provides a resource for the exploration of circulating miRNA profiles in SSc subtypes and RP.

INSTRUMENT(S): NextSeq 550

ORGANISM(S): Homo sapiens

SUBMITTER: Jacopo Sabbatinelli

PROVIDER: E-MTAB-16866 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:To investigate the miRNA signature in the serum of systemic sclerosis (SSc) patients. The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients as compared to 9 healthy controls by using an Openarray platform. Patients fulfilling the ACR/EULAR 2013 classification criteria were classified in relation to the extent of skin fibrosis as limited cutaneous (lcSSc) or diffuse cutaneous SSc (dcSSc); patients fulfilling the classification criteria without skin fibrosis will be referred to as non-cutaneous SSc (ncSSc). MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers and therapeutic targets in rheumatic diseases. Here, we investigated the miRNA signature in the serum of systemic sclerosis (SSc) patients and we further assessed their expression in early stages of the disease.The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients as compared to 9 healthy controls by using an Openarray platform. Three miRNAs were examined in an additional cohort of 107 SSc patients and 24 healthy donors by single qPCR. MiR-483-5p expression was further analysed in the serum of patients with localized scleroderma (LoS) (n=22), systemic lupus erythematosus (SLE) (n=33) and primary Sjögren’s syndrome (pSS) (n=23). The function of miR-483-5p was examined by transfecting miR-483-5p into primary human dermal fibroblasts and pulmonary endothelial cells.30 miRNAs were significantly increased in patients with SSc. Of these, miR-483-5p showed reproducibly higher levels in an independent SSc cohort and was also elevated in patients with preclinical-SSc symptoms (early SSc). Notably, miR-483-5p was not differentially expressed in patients with SLE or pSS, whereas it was up-regulated in LoS, indicating that this miRNA could be involved in the development of skin fibrosis. Consistently, miR-483-5p overexpression in fibroblasts and endothelial cells modulated the expression of fibrosis-related genes.Our findings showed that miR-483-5p is up-regulated in the serum of SSc patients, from the early stages of the disease onwards, and indicated its potential function as a fine regulator of fibrosis in SSc.

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Small RNA-seq analysis of serum miRNAs from patients with systemic sclerosis, Raynaud’s phenomenon, and healthy controls

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