{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:54:31Z","timestamp":1787032471557,"version":"build-2736575974"},"posted":{"date-parts":[[2025,12,18]]},"group-title":"Genomics","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"award":["Intramural Research Program"],"award-info":[{"award-number":["Intramural Research Program"]}],"id":[{"id":"https:\/\/ror.org\/006zn3t30","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Division of Intramural Research"],"award-info":[{"award-number":["Division of Intramural Research"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Glucocorticoids (GCs) are widely used anti-inflammatory and immunosuppressive agents known to induce dramatic changes in gene expression, yet their effects on non-coding RNAs such as long non-coding RNAs (lncRNAs) or microRNAs (miRNAs) remain poorly characterized. We present the first comprehensive and systematic analysis of GC regulation of the non-coding genome across nine human primary cell types from both hematopoietic and non-hematopoietic lineages. In vitro GC treatment was applied to each cell type, with transcriptomic profiling (total RNA-seq and small RNA-seq) at 2 and 6 hours post-treatment. We identified over 2,000 GC-responsive non-coding transcripts, including 654 annotated lncRNAs, 1,376 novel lncRNAs, and 39 miRNAs. The non-coding RNA response to GCs was highly cell type-dependent: 80% of GC-responsive lncRNAs and 97% of miRNAs were unique to a single cell type. Hematopoietic cells exhibited a greater magnitude of lncRNA induction than non-hematopoietic cells. Notably, dozens of facultative lncRNAs (undetectable at baseline) were induced de novo by GC. GC-responsive transcripts spanned diverse lncRNA classes, with enrichment of host lncRNAs. By contrast, only a limited number of miRNAs were GC-responsive. GC regulation of transcript abundance for miRNAs and their host lncRNAs appears to be independent. Our results, which are accessible through an interactive web application, establish a framework for studying how non-coding transcription contributes to physiological and clinical heterogeneity in GC responses. The newly identified GC-responsive non-coding transcripts could represent biomarkers of GC exposure, determinants of GC sensitivity or resistance, or candidate regulators of tissue-specific GC effects.<\/jats:p>","DOI":"10.64898\/2025.12.18.695158","type":"posted-content","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T08:25:16Z","timestamp":1766132716000},"source":"Crossref","is-referenced-by-count":1,"title":["Glucocorticoids regulate the human non-coding genome"],"prefix":"10.64898","author":[{"given":"Thai","family":"Tran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Kwiat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilin","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Skyler","family":"Kuhn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine N.","family":"Howe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manasi","family":"Gadkari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0540-5942","authenticated-orcid":false,"given":"Luis M.","family":"Franco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025122307100509000_2025.12.18.695158v1.1","unstructured":"Andrews, S. 2010. FastQC: a quality control tool for highthroughput sequence data."},{"key":"2025122307100509000_2025.12.18.695158v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07282-7"},{"key":"2025122307100509000_2025.12.18.695158v1.3","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0328com"},{"key":"2025122307100509000_2025.12.18.695158v1.4","doi-asserted-by":"crossref","first-page":"101949","DOI":"10.1016\/j.smim.2025.101949","article-title":"Endogenous glucocorticoids and human immunity: Time to revisit old dogmas","volume":"78","year":"2025","journal-title":"Semin Immunol"},{"key":"2025122307100509000_2025.12.18.695158v1.5","doi-asserted-by":"publisher","DOI":"10.1007\/BF01138177"},{"key":"2025122307100509000_2025.12.18.695158v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.1"},{"key":"2025122307100509000_2025.12.18.695158v1.7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2011.03514.x"},{"key":"2025122307100509000_2025.12.18.695158v1.8","doi-asserted-by":"crossref","first-page":"e22879","DOI":"10.1096\/fj.202201784R","article-title":"Glucocorticoid exposure modifies the miRNA profile of sperm in the guinea pig: Implications for intergenerational transmission","volume":"37","year":"2023","journal-title":"Faseb j"},{"key":"2025122307100509000_2025.12.18.695158v1.9","unstructured":"Chang, W. , Cheng, J. , Allaire, J. J. , Sievert, C. , Schloerke, B. , Xie, Y. , Allen, J. , Mcpherson, J. , Dipert, A. & Borges, B. 2025. shiny: Web Application Framework for R. 1.11.1 ed."},{"key":"2025122307100509000_2025.12.18.695158v1.10","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"2025122307100509000_2025.12.18.695158v1.11","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747044"},{"key":"2025122307100509000_2025.12.18.695158v1.12","first-page":"57","article-title":"Effects of allergic stimulation and glucocorticoids on miR-155 in CD4(+) T-cells","volume":"7","year":"2018","journal-title":"Am J Clin Exp Immunol"},{"key":"2025122307100509000_2025.12.18.695158v1.13","doi-asserted-by":"publisher","DOI":"10.1002\/art.37966"},{"key":"2025122307100509000_2025.12.18.695158v1.14","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2025122307100509000_2025.12.18.695158v1.15","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41584-024-01144-2","article-title":"Shedding light onto the immunometabolic effects of glucocorticoids","volume":"20","year":"2024","journal-title":"Nat Rev Rheumatol"},{"key":"2025122307100509000_2025.12.18.695158v1.16","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180595"},{"key":"2025122307100509000_2025.12.18.695158v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1394"},{"key":"2025122307100509000_2025.12.18.695158v1.18","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr688"},{"key":"2025122307100509000_2025.12.18.695158v1.19","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0245com"},{"key":"2025122307100509000_2025.12.18.695158v1.20","doi-asserted-by":"publisher","DOI":"10.1126\/science.3563523"},{"key":"2025122307100509000_2025.12.18.695158v1.21","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.7.13.8405814"},{"key":"2025122307100509000_2025.12.18.695158v1.22","doi-asserted-by":"crossref","unstructured":"Greulich, F. , Bielefeld, K. A. , Scheundel, R. , Mechtidou, A. , Strickland, B. & Uhlenhaut, N. H . 2021. Enhancer RNA Expression in Response to Glucocorticoid Treatment in Murine Macrophages. Cells, 11.","DOI":"10.3390\/cells11010028"},{"key":"2025122307100509000_2025.12.18.695158v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2013.106"},{"key":"2025122307100509000_2025.12.18.695158v1.24","doi-asserted-by":"publisher","DOI":"10.1101\/gr.135350.111"},{"key":"2025122307100509000_2025.12.18.695158v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2456"},{"key":"2025122307100509000_2025.12.18.695158v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/ng.759"},{"key":"2025122307100509000_2025.12.18.695158v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.07.002"},{"key":"2025122307100509000_2025.12.18.695158v1.28","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1141"},{"key":"2025122307100509000_2025.12.18.695158v1.29","unstructured":"Kuhn, S. & Zhang, G . 2024. OpenOmics\/mir-seek:v0.3.0. Zenodo version= v0.3.0."},{"key":"2025122307100509000_2025.12.18.695158v1.30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019536108"},{"key":"2025122307100509000_2025.12.18.695158v1.31","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31825b8ebc"},{"key":"2025122307100509000_2025.12.18.695158v1.32","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"2025122307100509000_2025.12.18.695158v1.33","doi-asserted-by":"crossref","first-page":"7454","DOI":"10.1038\/s41380-021-01274-z","article-title":"TCF7L2 lncRNA: a link between bipolar disorder and body mass index through glucocorticoid signaling","volume":"26","year":"2021","journal-title":"Mol Psychiatry"},{"key":"2025122307100509000_2025.12.18.695158v1.34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.gene.2018.01.089","article-title":"The expression profiling and ontology analysis of non-coding RNAs in dexamethasone induced steatosis in hepatoma cell","volume":"650","year":"2018","journal-title":"Gene"},{"key":"2025122307100509000_2025.12.18.695158v1.35","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2025122307100509000_2025.12.18.695158v1.36","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","year":"2011","journal-title":"EMBnet.journal"},{"key":"2025122307100509000_2025.12.18.695158v1.37","doi-asserted-by":"crossref","first-page":"8370","DOI":"10.1038\/s41598-019-44827-7","article-title":"lncRNA PSORS1C3 is regulated by glucocorticoids and fine-tunes OCT4 expression in non-pluripotent cells","volume":"9","year":"2019","journal-title":"Sci Rep"},{"key":"2025122307100509000_2025.12.18.695158v1.38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.015755"},{"key":"2025122307100509000_2025.12.18.695158v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/srep23002"},{"key":"2025122307100509000_2025.12.18.695158v1.40","doi-asserted-by":"crossref","unstructured":"Pertea, G. & Pertea, M . 2020. GFF Utilities: GffRead and GffCompare. F1000Res, 9.","DOI":"10.12688\/f1000research.23297.1"},{"key":"2025122307100509000_2025.12.18.695158v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3122"},{"key":"2025122307100509000_2025.12.18.695158v1.42","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1038\/s41598-018-19704-4","article-title":"Dexamethasone induced miR-155 up-regulation in differentiating 3T3-L1 preadipocytes does not affect adipogenesis","volume":"8","year":"2018","journal-title":"Sci Rep"},{"key":"2025122307100509000_2025.12.18.695158v1.43","doi-asserted-by":"crossref","unstructured":"Pierouli, K. , Papageorgiou, L. , Mitsis, T. , Papakonstantinou, E. , Diakou, I. , Leptidis, S. , Sigala, M. , Dragoumani, K. , Spandidos, D. A. , Bacopoulou, F. , Chrousos, G. P. , Goulielmos, G. , Eliopoulos, E. & Vlachakis, D . 2022. Role of microRNAs and long non-coding RNAs in glucocorticoid signaling (Review). Int J Mol Med, 50.","DOI":"10.3892\/ijmm.2022.5203"},{"key":"2025122307100509000_2025.12.18.695158v1.44","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201405010"},{"key":"2025122307100509000_2025.12.18.695158v1.45","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00762"},{"key":"2025122307100509000_2025.12.18.695158v1.46","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00062-12"},{"key":"2025122307100509000_2025.12.18.695158v1.47","doi-asserted-by":"publisher","DOI":"10.1101\/gr.2722704"},{"key":"2025122307100509000_2025.12.18.695158v1.48","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021115-105323"},{"key":"2025122307100509000_2025.12.18.695158v1.49","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026445108136"},{"key":"2025122307100509000_2025.12.18.695158v1.50","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019103777"},{"key":"2025122307100509000_2025.12.18.695158v1.51","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2663"},{"key":"2025122307100509000_2025.12.18.695158v1.52","doi-asserted-by":"crossref","first-page":"101424","DOI":"10.1016\/j.molmet.2021.101424","article-title":"Glucocorticoids coordinate macrophage metabolism through the regulation of the tricarboxylic acid cycle","volume":"57","year":"2022","journal-title":"Mol Metab"},{"key":"2025122307100509000_2025.12.18.695158v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.03.027"},{"key":"2025122307100509000_2025.12.18.695158v1.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2020.03.003"},{"key":"2025122307100509000_2025.12.18.695158v1.55","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080547"},{"key":"2025122307100509000_2025.12.18.695158v1.56","doi-asserted-by":"crossref","first-page":"565","DOI":"10.2174\/011574888X290779240521130244","article-title":"Long Non-coding RNA DANCR Regulates the Proliferation and Migration of Human Adipose-derived Mesenchymal Stromal Cells in Inflammation Conditions","volume":"20","year":"2025","journal-title":"Curr Stem Cell Res Ther"},{"key":"2025122307100509000_2025.12.18.695158v1.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.01.031"},{"key":"2025122307100509000_2025.12.18.695158v1.58","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000798"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2025.12.18.695158","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T15:19:58Z","timestamp":1766503198000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2025.12.18.695158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":58,"URL":"https:\/\/doi.org\/10.64898\/2025.12.18.695158","relation":{},"subject":[],"published":{"date-parts":[[2025,12,18]]},"subtype":"preprint"}}