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Non\u2010coding RNAs (ncRNAs) are key epigenetic regulators of pathological FLS activation; however, the field is constrained by three core limitations: fragmented evidence, mechanistic homogenization, and a persistent basic\u2010to\u2010clinical translational gap. Adopting a structured evidence\u2010grading narrative review framework, we systematically synthesize evidence on the regulatory roles of three major ncRNA classes (microRNAs [miRNAs], long ncRNAs [lncRNAs], and circular RNAs [circRNAs]) across four hallmark RA\u2010FLS pathophenotypes: proliferation\u2010apoptosis dysregulation, invasive matrix degradation, pro\u2010inflammatory secretion, and metabolic reprogramming, acting via diverse mechanisms including competitive endogenous RNA (ceRNA) sponging and epigenetic modification. We further integrated a panoramic cross\u2010class synergistic ceRNA regulatory network and identified 12 high\u2010confidence translational targets (prioritized by clinical, in\u00a0vivo, and primary cell multi\u2010level evidence, exemplified by miR\u2010124, miR\u2010146a, GAS5, and circFBXW7). We also synthesize current evidence on ncRNA biomarker utility, two canonical interventional paradigms (gain\u2010of\u2010function [GoF] and loss\u2010of\u2010function [LoF] strategies), and shared translational bottlenecks across the field. Collectively, ncRNA\u2010targeted stroma\u2010directed therapy emerges as a novel interventional paradigm for RA articular structural protection. Prioritized future directions include FLS subpopulation\u2010specific functional characterization, optimization of synovial\u2010targeted delivery systems, exploration of non\u2010canonical regulatory mechanisms, and multicenter validation of ncRNA\u2010based biomarkers to accelerate clinical translation.<\/jats:p>","DOI":"10.1111\/1756-185x.70922","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:40:33Z","timestamp":1792500033000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic Landscape and Therapeutic Opportunities of Non\u2010Coding\n                    <scp>RNAs<\/scp>\n                    in Modulating Fibroblast\u2010Like Synoviocytes in Rheumatoid Arthritis"],"prefix":"10.1111","volume":"29","author":[{"given":"Lei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Bone and Joint Surgery Orthopaedics Center The First Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9737-8628","authenticated-orcid":false,"given":"Fengping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bone and Joint Surgery Orthopaedics Center The First Hospital of Jilin University  Changchun 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