{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T23:49:30Z","timestamp":1773186570835,"version":"3.50.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2507605"],"award-info":[{"award-number":["2023YFC2507605"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Disuse osteoporosis (DOP) poses a significant health risk during extended space missions. Although the importance of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cells (BMSCs) and orthopedic diseases is recognized, the precise mechanism by which lncRNAs contribute to DOP remains elusive. This research aims to elucidate the potential regulatory role of lncRNAs in DOP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sequencing data were obtained from Gene Expression Omnibus (GEO) datasets, including coding and non-coding RNAs. Positive co-expression pairs of lncRNA-mRNA were identified using weighted gene co-expression network analysis, while miRNA-mRNA expression pairs were derived from the prediction database. A mRNA-miRNA-lncRNA network was established according to the shared mRNA. Functional enrichment analysis was conducted for the shared mRNAs using genome ontology and KEGG pathways. Hub genes were identified through protein-protein interaction analysis, and connectivity map analysis was employed to identify potential therapeutic agents for DOP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Integration of 74 lncRNAs, 19 miRNAs, and 200 mRNAs yielded a comprehensive mRNA-miRNA-lncRNA network. Enrichment analysis highlighted endoplasmic reticulum stress and extracellular matrix (ECM) pathways as significant in the ceRNA network. PPI analysis revealed three hub genes (COL4A1, LAMC1, and LAMA4) and identified five lncRNA-miRNA-hub gene regulatory axes. Furthermore, three potential therapeutic compounds (SB-216763, oxymetholone, and flubendazole) for DOP were identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study sheds light on the involvement of lncRNAs in the pathogenesis and treatment of DOP through the construction of a ceRNA network, linking protein-coding mRNA functions with non-coding RNAs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1444165","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T05:16:22Z","timestamp":1743657382000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Deciphering the role of lncRNA-mediated ceRNA network in disuse osteoporosis: insights from bone marrow mesenchymal stem cells under simulated microgravity"],"prefix":"10.3389","volume":"12","author":[{"given":"Wuzeng","family":"Wei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.bone.2015.12.057","article-title":"The impact of microgravity on bone in humans.","volume":"87","author":"Grimm","year":"2016","journal-title":"Bone."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1016\/S0273-1177(03)90395-4","article-title":"Microgravity and bone cell mechanosensitivity.","volume":"32","author":"Klein-Nulend","year":"2003","journal-title":"Adv Space Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1152\/japplphysiol.01209.2007","article-title":"Food restriction and simulated microgravity: Effects on bone and serum leptin.","volume":"104","author":"Baek","year":"1985","journal-title":"J Appl Physiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1159\/000252852","article-title":"Space, gravity and the physiology of aging: Parallel or convergent disciplines? A mini-review.","volume":"56","author":"Vernikos","year":"2010","journal-title":"Gerontology."},{"key":"B5","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/j.jbspin.2011.04.007","article-title":"Pathophysiology of bone loss in disuse osteoporosis.","volume":"78","author":"Alexandre","year":"2011","journal-title":"Joint Bone Spine."},{"key":"B6","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage potential of adult human mesenchymal stem cells.","volume":"284","author":"Pittenger","year":"1999","journal-title":"Science."},{"key":"B7","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3727\/096368910X","article-title":"Mesenchymal stem cells.","volume":"20","author":"Ding","year":"2011","journal-title":"Cell Transplant."},{"key":"B8","doi-asserted-by":"publisher","first-page":"507301","DOI":"10.1155\/2013\/507301","article-title":"Prospective isolation of murine and human bone marrow mesenchymal stem cells based on surface markers.","volume":"2013","author":"Mabuchi","year":"2013","journal-title":"Stem Cells Int."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1038\/cdd.2015.168","article-title":"Fate decision of mesenchymal stem cells: Adipocytes or osteoblasts?","volume":"23","author":"Chen","year":"2016","journal-title":"Cell Death Differ."},{"key":"B10","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/nrg2521","article-title":"Long non-coding RNAs: Insights into functions.","volume":"10","author":"Mercer","year":"2009","journal-title":"Nat Rev Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"3387","DOI":"10.1073\/pnas.1222643110","article-title":"Long noncoding RNAs regulate adipogenesis.","volume":"110","author":"Sun","year":"2013","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1002\/jcp.25688","article-title":"Mechanical stress regulates bone metabolism through MicroRNAs.","volume":"232","author":"Yuan","year":"2017","journal-title":"J Cell Physiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.cell.2011.07.014","article-title":"A ceRNA hypothesis: The Rosetta Stone of a hidden RNA language?","volume":"146","author":"Salmena","year":"2011","journal-title":"Cell."},{"key":"B14","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/nbt0308-303","article-title":"What is principal component analysis?","volume":"26","author":"Ringn\u00e9r","year":"2008","journal-title":"Nat Biotechnol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1104\/pp.110.159459","article-title":"The association of multiple interacting genes with specific phenotypes in rice using gene coexpression networks.","volume":"154","author":"Ficklin","year":"2010","journal-title":"Plant Physiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1126\/science.1132939","article-title":"The connectivity map: Using gene-expression signatures to connect small molecules, genes, and disease.","volume":"313","author":"Lamb","year":"2006","journal-title":"Science."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2858","DOI":"10.1096\/fj.11-0902ufm","article-title":"To infinity and beyond! Human spaceflight and life science.","volume":"25","author":"Hughes-Fulford","year":"2011","journal-title":"FASEB J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"194417","DOI":"10.1016\/j.bbagrm.2019.194417","article-title":"Non-coding RNA regulatory networks.","volume":"1863","author":"Panni","year":"2020","journal-title":"Biochim Biophys Acta Gene Regul Mech."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1126\/science.1209038","article-title":"The unfolded protein response: From stress pathway to homeostatic regulation.","volume":"334","author":"Walter","year":"2011","journal-title":"Science."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.bone.2016.12.009","article-title":"Role of endoplasmic reticulum stress in disuse osteoporosis.","volume":"97","author":"Li","year":"2017","journal-title":"Bone."},{"key":"B21","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/s0006-291x(03)01165-3","article-title":"Cell shape provides global control of focal adhesion assembly.","volume":"307","author":"Chen","year":"2003","journal-title":"Biochem Biophys Res Commun."},{"key":"B22","doi-asserted-by":"publisher","first-page":"C1411","DOI":"10.1152\/ajpcell.00098.2002","article-title":"Early activation of p160ROCK by pressure overload in rat heart.","volume":"284","author":"Torsoni","year":"2003","journal-title":"Am J Physiol Cell Physiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1161\/01.res.87.7.558","article-title":"Early activation of the multicomponent signaling complex associated with focal adhesion kinase induced by pressure overload in the rat heart.","volume":"87","author":"Franchini","year":"2000","journal-title":"Circ Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"3819","DOI":"10.1016\/j.yexcr.2007.07.038","article-title":"Laminin isoforms and their integrin receptors in glioma cell migration and invasiveness: Evidence for a role of alpha5-laminin(s) and alpha3beta1 integrin.","volume":"313","author":"Kawataki","year":"2007","journal-title":"Exp Cell Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.exger.2014.07.020","article-title":"Discovery and characterization of miRNA during cellular senescence in bone marrow-derived human mesenchymal stem cells.","volume":"58","author":"Yoo","year":"2014","journal-title":"Exp Gerontol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.matbio.2018.01.007","article-title":"Bone marrow laminins influence hematopoietic stem and progenitor cell cycling and homing to the bone marrow.","volume":"67","author":"Susek","year":"2018","journal-title":"Matrix Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"a031229","DOI":"10.1101\/cshperspect.a031229","article-title":"Mechanism of bone mineralization.","volume":"8","author":"Murshed","year":"2018","journal-title":"Cold Spring Harb Perspect Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.biocel.2015.05.008","article-title":"Extracellular matrix networks in bone remodeling.","volume":"65","author":"Alford","year":"2015","journal-title":"Int J Biochem Cell Biol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e1007378","DOI":"10.1371\/journal.pgen.1007378","article-title":"LncRNA Jpx induces Xist expression in mice using both trans and cis mechanisms.","volume":"14","author":"Carmona","year":"2018","journal-title":"PLoS Genet."},{"key":"B30","doi-asserted-by":"publisher","first-page":"803","DOI":"10.3892\/etm.2018.7033","article-title":"Long non-coding RNA XIST promotes osteoporosis through inhibiting bone marrow mesenchymal stem cell differentiation.","volume":"17","author":"Chen","year":"2019","journal-title":"Exp Ther Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1080\/03008207.2020.1752200","article-title":"Downregulation of lncRNA XIST promotes proliferation and differentiation, limits apoptosis of osteoblasts through regulating miR-203-3p\/ZFPM2 axis.","volume":"62","author":"Niu","year":"2021","journal-title":"Connect Tissue Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"643","DOI":"10.21037\/atm.2019.10.71","article-title":"miR-3619-3p promotes papillary thyroid carcinoma progression via Wnt\/\u03b2-catenin pathway.","volume":"7","author":"Yu","year":"2019","journal-title":"Ann Transl Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s13045-019-0773-y","article-title":"LINC01123, a c-Myc-activated long non-coding RNA, promotes proliferation and aerobic glycolysis of non-small cell lung cancer through miR-199a-5p\/c-Myc axis.","volume":"12","author":"Hua","year":"2019","journal-title":"J Hematol Oncol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"10116","DOI":"10.18632\/aging.102424","article-title":"The construction and analysis of tumor-infiltrating immune cell and ceRNA networks in recurrent soft tissue sarcoma.","volume":"11","author":"Huang","year":"2019","journal-title":"Aging (Albany NY)."},{"key":"B35","doi-asserted-by":"publisher","first-page":"428","DOI":"10.3389\/fbioe.2020.00428","article-title":"Let-7i-5p regulation of cell morphology and migration through distinct signaling pathways in normal and pathogenic urethral fibroblasts.","volume":"8","author":"Zhang","year":"2020","journal-title":"Front Bioeng Biotechnol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"115153","DOI":"10.1016\/j.bone.2019.115153","article-title":"Inhibition of osteoclasts differentiation by CDC2-induced NFATc1 phosphorylation.","volume":"131","author":"Kim","year":"2020","journal-title":"Bone."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2388","DOI":"10.1074\/jbc.M406294200","article-title":"Glucocorticoids inhibit the transcriptional activity of LEF\/TCF in differentiating osteoblasts in a glycogen synthase kinase-3beta-dependent and -independent manner.","volume":"280","author":"Smith","year":"2005","journal-title":"J Biol Chem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1007\/s00774-008-0019-5","article-title":"Glucocorticoid induces apoptosis of osteoblast cells through the activation of glycogen synthase kinase 3beta.","volume":"27","author":"Yun","year":"2009","journal-title":"J Bone Miner Metab."},{"key":"B39","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1002\/ptr.6817","article-title":"Fructus ligustri lucidi preserves bone quality through induction of canonical Wnt\/\u03b2-catenin signaling pathway in ovariectomized rats.","volume":"35","author":"Liu","year":"2021","journal-title":"Phytother Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"115333","DOI":"10.1016\/j.taap.2020.115333","article-title":"Daphnetin ameliorates glucocorticoid-induced osteoporosis via activation of Wnt\/GSK-3\u03b2\/\u03b2-catenin signaling.","volume":"409","author":"Wang","year":"2020","journal-title":"Toxicol Appl Pharmacol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1093\/geronj\/33.2.204","article-title":"Effect of sodium fluoride, inorganic phosphate, and oxymetholone therapies in osteoporosis: A six-year progress report.","volume":"33","author":"Vose","year":"1978","journal-title":"J Gerontol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/nrc1317","article-title":"Microtubules as a target for anticancer drugs.","volume":"4","author":"Jordan","year":"2004","journal-title":"Nat Rev Cancer."},{"key":"B43","doi-asserted-by":"publisher","first-page":"8080","DOI":"10.7150\/thno.43473","article-title":"Flubendazole elicits anti-cancer effects via targeting EVA1A-modulated autophagy and apoptosis in Triple-negative breast cancer.","volume":"10","author":"Zhen","year":"2020","journal-title":"Theranostics."},{"key":"B44","doi-asserted-by":"publisher","first-page":"105305","DOI":"10.1016\/j.phrs.2020.105305","article-title":"Flubendazole, FDA-approved anthelmintic, elicits valid antitumor effects by targeting P53 and promoting ferroptosis in castration-resistant prostate cancer.","volume":"164","author":"Zhou","year":"2021","journal-title":"Pharmacol Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"109769","DOI":"10.1016\/j.biopha.2019.109769","article-title":"Vinpocetine inhibits RANKL-induced osteoclastogenesis and attenuates ovariectomy-induced bone loss.","volume":"123","author":"Zhu","year":"2020","journal-title":"Biomed Pharmacother."},{"key":"B46","doi-asserted-by":"publisher","first-page":"627","DOI":"10.4269\/ajtmh.1984.33.627","article-title":"Treatment of neurocysticercosis with flubendazole.","volume":"33","author":"T\u00e9llez-Gir\u00f3n","year":"1984","journal-title":"Am J Trop Med Hyg."},{"key":"B47","first-page":"185","article-title":"Flubendazole versus mebendazole in intestinal helminthic infections.","volume":"39","author":"Feldmeier","year":"1982","journal-title":"Acta Trop."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1444165\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T05:16:25Z","timestamp":1743657385000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1444165\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,3]]},"references-count":47,"alternative-id":["10.3389\/fmed.2025.1444165"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1444165","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,3]]},"article-number":"1444165"}}