Identification of serum exosomal lncRNAs and their potential regulation of characteristic genes of fibroblast-like synoviocytes in rheumatoid arthritis.

Autor: Zhou TS; School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei 230032, China; The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei 230022, China., Yang CL; School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei 230032, China; The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei 230022, China., Wang JQ; Department of Pharmacy, Affiliated Psychological Hospital of Anhui Medical University, Hefei 230000, China; Department of Pharmacy, Hefei Fourth People's Hospital, Hefei 230000, China; Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei 230000, China., Fang L; School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei 230032, China; The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei 230022, China., Xia Q; School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei 230032, China; The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei 230022, China. Electronic address: xiaquan2010@163.com., Liu YR; School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei 230032, China; The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei 230022, China. Electronic address: liuyaru@ahmu.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 25; Vol. 143 (Pt 2), pp. 113382. Date of Electronic Publication: 2024 Oct 20.
DOI: 10.1016/j.intimp.2024.113382
Abstrakt: Rheumatoid arthritis (RA) is a common autoimmune disease whose pathogenesis is poorly understand. Gaps in laboratory biomarkers cause a lack of clinically available strategies for the early diagnosis and treatment of RA. This study aims to identify serum exosomal lncRNAs as promising biomarkers and to unravel potential mechanisms by which they affect characteristic genes of fibroblast-like synoviocytes (FLSs) to induce RA malignant properties. RNA sequencing datasets of serum exosomes (GSE271161 and PRJNA911001) and FLSs (GSE103578, GSE122616, GSE128813, GSE181614 and GSE83147) were purposively mined. Visualization and functional enrichment of differentially expressed (DE) lncRNAs/protein-coding genes, screening of significant lncRNAs, and construction of competing endogenous RNAs (ceRNAs) and protein-protein interaction (PPI) network were carried out. Quantitative real-time PCR, receiver operating characteristic curve (ROC) and correlation analysis were conducted on the validation cohort. As a result, we screened a total of 131 serum exosomal DElncRNAs and 125 FLSs DEmRNAs, which were predominantly enriched in the proliferative, inflammatory and metabolic pathways. In-depth learning of DElncRNAs expression profiles was performed to identify models with better performance and lncRNAs with higher importance scores using 4 machine learning algorithms (SVM, KNN, RF, Logit), which led to the establishment of ceRNAs network linking serum exosomal lncRNAs and characteristic genes of FLSs. In short, we proposed that 4 RA-representative serum exosomal lncRNAs (DLEU2, FAM13A-AS1, MEG3 and SNHG15) may be applied as valuable indicators for laboratory tests, and their-mediated intercellular communication and ceRNAs network may regulate the characteristic genes of FLSs, thereby generating malignant phenotypes and adaptive synovial microenvironment in RA.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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