{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T23:06:03Z","timestamp":1784243163293,"version":"3.55.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Osteoarthritis (OA) and type 2 diabetes mellitus (T2DM) frequently coexist and share inflammatory and metabolic disturbances, but the immune-epigenetic features that may overlap between these conditions remain incompletely defined. Enhancer RNAs (eRNAs) are increasingly recognized as regulators of enhancer activity and transcriptional programs, whereas eRNA-associated signatures shared between OA-related and T2DM-related datasets remain largely unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Transcriptomic datasets from OA joint tissues and controls (63 OA, 35 controls) were analyzed together with an independent T2DM dataset of CD14\n                      <jats:sup>+<\/jats:sup>\n                      monocytes (5 T2DM, 5 controls) to explore overlapping molecular features across distinct disease-related contexts. Differential expression analysis, exploratory Weighted Gene Co-expression Network Analysis (WGCNA), CIBERSORT-based estimation, and pathway analyses were used to prioritize eRNA-associated features, transcription factors (TFs), candidate genes, and immune-associated transcriptional patterns. Public ATAC-seq, ChIP-seq, and scRNA-seq datasets, together with a high-glucose stress model in rat chondrocytes, were used to provide epigenomic, cellular, and preliminary experimental context for the candidate associations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 473 annotated dysregulated eRNA-associated features in OA, with associated genes enriched in skeletal development, extracellular matrix remodeling, and PI3K-Akt signaling. CIBERSORT-based and pathway analyses suggested immune-associated transcriptional alterations and inflammatory pathway activation in OA. Integrative analysis prioritized TOB1 as a candidate eRNA-associated feature related to JUN,\n                      <jats:italic>CCNL1<\/jats:italic>\n                      , and inflammatory signaling within an inferred correlation-based network. Public ATAC-seq, ChIP-seq, and scRNA-seq datasets provided supportive epigenomic and cellular context for these candidate associations. Comparison with the T2DM monocyte dataset showed overlapping TNF-\u03b1\/NF-\u03baB and MAPK-related pathway alterations, with CCNL1 identified as a commonly downregulated candidate gene.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , high-glucose stress was accompanied by reduced TOB1, JUN, and CCNL1 protein levels and increased TNF-\u03b1 expression in chondrocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      TOB1 was prioritized as a candidate eRNA-associated signal related to JUN,\n                      <jats:italic>CCNL1<\/jats:italic>\n                      , and inflammatory signaling across OA-related and T2DM-related datasets. These findings provide a bioinformatics-driven and correlation-based framework supported by public epigenomic context and preliminary\n                      <jats:italic>in vitro<\/jats:italic>\n                      data, offering potential directions for future studies of immune-metabolic overlap between OA and T2DM.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1875546","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T22:10:11Z","timestamp":1784239811000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated multi-omics analysis identifies candidate eRNA-associated signatures shared between osteoarthritis and type 2 diabetes"],"prefix":"10.3389","volume":"17","author":[{"given":"Danni","family":"Huang","sequence":"first","affiliation":[{"name":"Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University","place":["Guangzhou, Guangdong Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junying","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Jiangmen Central Hospital","place":["Jiangmen, Guangdong Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Third Hospital of Xiamen","place":["Xiamen, Fujian Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University","place":["Guangzhou, Guangdong Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University","place":["Guangzhou, Guangdong Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"377","DOI":"10.3389\/fcell.2019.00377","article-title":"Diversity and emerging roles of enhancer RNA in regulation of gene expression and cell fate","volume":"7","author":"Arnold","year":"2019","journal-title":"Front. 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