{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:53:54Z","timestamp":1789386834774,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,3,21]],"date-time":"2021-03-21T00:00:00Z","timestamp":1616284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the regulatory network of long non\u2010coding RNA (lncRNA) as competing endogenous RNAs (ceRNAs) in osteonecrosis of the femoral head (ONFH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The gene expression profile GSE74089 of ONFH and microRNA (miRNA) expression profile of GSE89587 were obtained from the Gene Expression Omnibus (GEO) database. The GSE74089 contained four ONFH samples and four controls. The GSE89587 included 10 ONFH samples and 10 control samples. The differentially expressed lncRNAs (DE\u2010lncRNAs) and DE\u2010mRNAs between ONFH group and control group were identified from GSE74089 using the limma package based on criteria of adjusted <jats:italic>P<\/jats:italic> value &lt;0.05 and |log fold change (FC)| \u22652. The DEmiRNAs between ONFH group and control group were screened from GSE89587 on the basis of adjusted <jats:italic>P<\/jats:italic> value &lt;0.05. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway for DE\u2010mRNAs were analyzed using DAVID 6.7 and GSEA 3.0, respectively. Coexpressed lncRNA\u2010mRNA pairs were identified by corr.test method in R based on the criteria of adjusted <jats:italic>P<\/jats:italic> value &lt;0.01 and |r|\u2009\u2265\u20090.9. A ceRNA network was constructed and visualized using cytoscape 3.7.0 by integrating the DE\u2010lncRNA, DE\u2010miRNA, and DEmRNA data. The key mRNAs and lncRNAs in the ceRNA network were further validated in an independent dataset of GSE123568.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Based on our analysis, a total of 28 DE\u2010lncRNAs, 1403 DE\u2010mRNAs, and 134 DE\u2010miRNAs were identified, respectively. The DE\u2010mRNAs were significantly enriched in the function of \u201cskeletal system development,\u201d \u201ccollagen fibril organization,\u201d \u201cblood vessel development,\u201d and \u201cregulation of nervous system development.\u201d Besides, 72 KEGG pathways, including eight active pathways and 64 suppressed pathways were identified, including which immune pathway was the most significantly activated one and which ribosome\u2010related function was the most suppressed. A co\u2010expression network including 161 DE\u2010mRNAs and 16 DE\u2010lncRNAs was built. Highly connected nodes were identified among lncRNAs such as <jats:italic>H19<\/jats:italic>, <jats:italic>C20orf203<\/jats:italic>, <jats:italic>LINC00355<\/jats:italic>, <jats:italic>SFTA3<\/jats:italic>, <jats:italic>CRNDE<\/jats:italic>, <jats:italic>CASC2<\/jats:italic>, <jats:italic>LINC00494<\/jats:italic>, <jats:italic>C9orf163<\/jats:italic>, <jats:italic>C10orf91<\/jats:italic>, and <jats:italic>LINC00301<\/jats:italic>. The ceRNA network indicated that lncRNA <jats:italic>H19<\/jats:italic> functioned as a ceRNA of hsa\u2010miR\u2010519b\u20103p and hsa\u2010miR\u2010296\u20105p in <jats:italic>ANKH<\/jats:italic> and <jats:italic>ECHDC1<\/jats:italic> regulation; lncRNA <jats:italic>C9orf163<\/jats:italic> functioned as a ceRNA of hsa\u2010miR\u2010424\u20105p in <jats:italic>CCNT1<\/jats:italic> regulation. The expression trends of <jats:italic>ANKH<\/jats:italic>, <jats:italic>CCNT1<\/jats:italic>, and <jats:italic>C9orf163<\/jats:italic> were successfully validated in independent dataset of GSE123568.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The ceRNAs of lncRNA <jats:italic>H19<\/jats:italic>\u2010 hsa\u2010miR\u2010519b\u20103p\/hsa\u2010miR\u2010296\u20105p\u2010<jats:italic>ANKH<\/jats:italic> and lncRNA <jats:italic>c9orf163\u2010<\/jats:italic> hsa\u2010miR\u2010424\u20105p\u2010<jats:italic>CCNT1<\/jats:italic> might play important roles in ONFH development. Our research provided an understanding of the important role of lncRNA\u2013related ceRNAs in ONFH.<\/jats:p><\/jats:sec>","DOI":"10.1111\/os.12834","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T04:16:24Z","timestamp":1616386584000},"page":"1067-1076","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Non\u2010coding <scp>RNA<\/scp> Identification in Osteonecrosis of the Femoral Head Using Competitive Endogenous <scp>RNA<\/scp> Network Analysis"],"prefix":"10.1111","volume":"13","author":[{"given":"Ning","family":"Han","sequence":"first","affiliation":[{"name":"Department of Emergency Trauma Surgery Shanghai East Hospital of Tongji University  Shanghai 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