{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T19:27:08Z","timestamp":1783366028636,"version":"3.54.6"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"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. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Diabetes mellitus is a major independent determinant of cardiovascular morbidity. Therefore, we evaluated whether a molecular RNA panel comprising\n                      <jats:italic>FZD5<\/jats:italic>\n                      and\n                      <jats:italic>GTF2I<\/jats:italic>\n                      could facilitate the early detection and discrimination of ischemic heart disease in individuals with type 2 diabetes mellitus.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We implemented a two-stage bioinformatics workflow to identify and validate two mRNA candidates associated with T2DM and IHD. Subsequently, we delineated non-coding RNAs linked to these transcripts and the pathways potentially implicated in T2DM complicated by IHD. Finally, we conducted a pilot case\u2013control study and quantified the panel members by RT-qPCR in 56 patients with T2DM, 25 with IHD, 26 with combined T2DM+IHD, and 60 matched controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Differential expression analysis showed upregulation of hsa-miR-1976,\n                      <jats:italic>FZD5<\/jats:italic>\n                      , and\n                      <jats:italic>GTF2I<\/jats:italic>\n                      , accompanied by downregulation of\n                      <jats:italic>LINC02210<\/jats:italic>\n                      in the T2DM+IHD group versus controls. The RNA panel achieved high discriminatory performance (AUC = 0.94) between T2DM+IHD and controls, highlighting its potential as a discriminatory tool.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      this study identified clinically relevant non-coding RNA\u2013based angiogenesis panel (\n                      <jats:italic>FZD5<\/jats:italic>\n                      ,\n                      <jats:italic>GTF2I<\/jats:italic>\n                      mRNAs, hsa-miR-1976 and\n                      <jats:italic>LINC02210<\/jats:italic>\n                      lncRNA) as a biomarker signature associated with type 2 diabetes mellitus complicated by ischemic heart disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1687145","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T05:24:50Z","timestamp":1761888290000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic\/epigenetic RNA dysregulation in type 2 diabetes mellitus complicated with ischemic heart disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Eslam S.","family":"Sedkey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Matboli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed G.","family":"Seadawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa G.A.","family":"Hegazy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102201","article-title":"Ferroptosis: Mechanisms and role in diabetes mellitus and its complications","author":"Liu","year":"2024","journal-title":"Aging research review"},{"key":"B2","unstructured":"2024"},{"key":"B3","unstructured":"2025"},{"key":"B4","unstructured":"Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes\n          \n          2021"},{"key":"B5","doi-asserted-by":"publisher","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1131171","article-title":"Analysis of mRNA-miRNA lncRNA differential expression in prediabetes\/type 2 diabetes mellitus patients as potential players in insulin resistance","volume":"14","author":"Ali","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2024110964","article-title":"Integrating transcriptomics and proteomics to understand the molecular mechanisms underlying the pathogenesis of type 2 diabetes mellitus","volume":"16","author":"Wei","year":"2024","journal-title":"Genomics"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.45835","article-title":"Cardiovascular complications of diabetes: from microvascular to macrovascular pathways","volume":"15","author":"Zakir","year":"2023","journal-title":"Cureus"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-022-05731-4","article-title":"Precision prognostics for the development of complications in diabetes","volume":"65","author":"Schiborn","year":"2022","journal-title":"Diabetologia"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14020428","article-title":"The triad of risk: linking MASLD, cardiovascular disease and type 2 diabetes; 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