Τίτλος:
Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background: MicroRNAs (miRNAs) in circulation have emerged as promising biomarkers. In this study, we aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients and in combination with bioinformatics analysis to evaluate the utility of selected differentially expressed miRNAs in the serum as potential OA biomarkers. Methods: Serum samples were collected from 12 primary OA patients, and 12 healthy individuals were screened using the Agilent Human miRNA Microarray platform interrogating 2549 miRNAs. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by quantitative real-time PCR (qRT-PCR) in all serum and in articular cartilage samples from OA patients (n= 12) and healthy individuals (n= 7). Bioinformatics analysis was used to investigate the involved pathways and target genes for the above miRNAs. Results: We identified 279 differentially expressed miRNAs in the serum of OA patients compared to controls. Two hundred and five miRNAs (73.5%) were upregulated and 74 (26.5%) downregulated. ROC analysis revealed that 77 miRNAs had area under the curve (AUC) > 0.8 and p< 0.05. Bioinformatics analysis in the 77 miRNAs revealed that their target genes were involved in multiple signaling pathways associated with OA, among which FoxO, mTOR, Wnt, pI3K/akt, TGF-β signaling pathways, ECM-receptor interaction, and fatty acid biosynthesis. qRT-PCR validation in seven selected out of the 77 miRNAs revealed 3 significantly downregulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p, and hsa-miR-140-3p) in the serum of OA patients, which were in silico predicted to be enriched in pathways involved in metabolic processes. Target-gene analysis of hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671-3p revealed that InsR and IGFR1 were common targets of all three miRNAs, highlighting their involvement in regulation of metabolic processes that contribute to OA pathology. Hsa-miR-140-3p and hsa-miR-671-3p expression levels were consistently downregulated in articular cartilage of OA patients compared to healthy individuals. Conclusions: A serum miRNA signature was established for the first time using high density resolution miR-arrays in OA patients. We identified a three-miRNA signature, hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-33b-3p, in the serum of OA patients, predicted to regulate metabolic processes, which could serve as a potential biomarker for the evaluation of OA risk and progression. © 2017 The Author(s).
Συγγραφείς:
Ntoumou, E.
Tzetis, M.
Braoudaki, M.
Lambrou, G.
Poulou, M.
Malizos, K.
Stefanou, N.
Anastasopoulou, L.
Tsezou, A.
Περιοδικό:
Clinical Epigenetics
Εκδότης:
BioMed Central Ltd.
Λέξεις-κλειδιά:
fatty acid; mammalian target of rapamycin; microRNA; microRNA 140; microRNA 33; microRNA 671; transcription factor FKHR; transforming growth factor beta; unclassified drug; Wnt protein; microRNA; Mirn140 microRNA, human; MIRN33 microRNA, human; MIRN671 microRNA, human, aged; area under the curve; Article; articular cartilage; bioinformatics; bone radiography; chondrocyte; clinical article; controlled study; down regulation; fatty acid synthesis; female; gene targeting; human; male; osteoarthritis; priority journal; receiver operating characteristic; reverse transcription polymerase chain reaction; upregulation; biology; blood; DNA microarray; down regulation; gene expression profiling; gene expression regulation; gene regulatory network; genetic marker; genetics; middle aged; osteoarthritis; procedures; sensitivity and specificity, Aged; Computational Biology; Down-Regulation; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Genetic Markers; Humans; Male; MicroRNAs; Middle Aged; Oligonucleotide Array Sequence Analysis; Osteoarthritis; Sensitivity and Specificity
DOI:
10.1186/s13148-017-0428-1
