{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:55:04Z","timestamp":1792079704333,"version":"4.4.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"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><jats:title>Background<\/jats:title><jats:p>The liver is the only organ that can completely regenerate after various injuries or tissue loss. There are still a large number of gene functions in liver regeneration that have not been explored. This study aimed to identify key genes in the early stage of liver regeneration in mice after partial hepatectomy (PH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We first analyzed the expression profiles of genes in mouse liver at 48 and 72 h after PH from Gene Expression Omnibus (GEO) database. Gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein\u2013protein interaction (PPI) analysis were performed to identify key genes in liver regeneration. Finally, we validated key genes <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 46 upregulated genes and 19 downregulated genes at 48 h after PH, and 223 upregulated genes and 40 downregulated genes at 72 h after PH, respectively. These genes were mainly involved in cell cycle, DNA replication, and p53 signaling pathway. Among of these genes, cycle-related genes (Ccna2, Cdkn1a, Chek1, and Mcm5) and Ube2c were highly expressed in the residual liver both at 48 and 72 h after PH. Furthermore, Ube2c knockdown not only caused abnormal expression of Ccna2, Cdkn1a, Chek1, and Mcm5, but also inhibited transition of hepatocytes from G1 to S phase of the cell cycle <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Mouse hepatocytes enter the proliferation phase at 48 h after PH. Ube2c may mediate cell proliferation by regulating or partially regulating Ccna2, Cdkn1a, Chek1, and Mcm5.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2021.670706","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T04:59:14Z","timestamp":1624424354000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Identifying the Key Genes in Mouse Liver Regeneration After Partial Hepatectomy by Bioinformatics Analysis and in vitro\/vivo Experiments"],"prefix":"10.3389","volume":"12","author":[{"given":"Jian","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Zhe","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Peng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Yong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"13599","DOI":"10.3748\/wjg.v20.i37.13599","article-title":"Laparoscopic liver resection for malignancy: a review of the literature.","volume":"20","author":"Alkhalili","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1002\/emmm.201000085","article-title":"Regulation of liver regeneration by growth factors and cytokines.","volume":"2","author":"Bohm","year":"2010","journal-title":"EMBO Mol. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1007\/s10549-007-9673-x","article-title":"Prediction of metastatic relapse in node-positive breast cancer: establishment of a clinicogenomic model after FEC100 adjuvant regimen.","volume":"109","author":"Campone","year":"2008","journal-title":"Breast Cancer Res. Treat."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1038\/ng1861","article-title":"A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers.","volume":"38","author":"Carter","year":"2006","journal-title":"Nat. Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1007\/s12031-019-01400-1","article-title":"PBK as a Potential Biomarker Associated with Prognosis of Glioblastoma.","volume":"70","author":"Dong","year":"2020","journal-title":"J. Mol. Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1053\/j.gastro.2014.08.045","article-title":"Challenges to liver transplantation and strategies to improve outcomes.","volume":"148","author":"Dutkowski","year":"2015","journal-title":"Gastroenterology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"S45","DOI":"10.1002\/hep.20969","article-title":"Liver regeneration.","volume":"43","author":"Fausto","year":"2006","journal-title":"Hepatology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3171","DOI":"10.3892\/or.2018.6766","article-title":"Downregulation of miR2245p in prostate cancer and its relevant molecular mechanism via TCGA. GEO database and in silico analyses.","volume":"40","author":"Gan","year":"2018","journal-title":"Oncol. Rep."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.223123","article-title":"Chk1-mediated Cdc25A degradation as a critical mechanism for normal cell cycle progression.","volume":"132","author":"Goto","year":"2019","journal-title":"J. Cell Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1016\/j.ymthe.2017.04.016","article-title":"lncRNA HOXD-AS1 Regulates Proliferation and Chemo-Resistance of Castration-Resistant Prostate Cancer via Recruiting WDR5.","volume":"25","author":"Gu","year":"2017","journal-title":"Mol. Ther."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1084\/jem.20092434","article-title":"Tob1 is a constitutively expressed repressor of liver regeneration.","volume":"207","author":"Ho","year":"2010","journal-title":"J. Exp. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"7833","DOI":"10.1002\/cam4.2630","article-title":"Anticancer effect of icaritin on prostate cancer via regulating miR-381-3p and its target gene UBE2C.","volume":"8","author":"Hu","year":"2019","journal-title":"Cancer Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1615\/CritRevEukaryotGeneExpr.2020029243","article-title":"The Identification of Key Gene Expression Signature in Prostate Cancer.","volume":"30","author":"Huang","year":"2020","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"key":"B14","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.suronc.2017.05.001","article-title":"Portal vein ligation versus portal vein embolization for induction of hypertrophy of the future liver remnant: A systematic review and meta-analysis.","volume":"26","author":"Isfordink","year":"2017","journal-title":"Surg. Oncol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/nature17039","article-title":"Reparative inflammation takes charge of tissue regeneration.","volume":"529","author":"Karin","year":"2016","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2744","DOI":"10.1158\/1078-0432.CCR-15-2119","article-title":"Cotargeting Androgen Receptor Splice Variants and mTOR Signaling Pathway for the Treatment of Castration-Resistant Prostate Cancer.","volume":"22","author":"Kato","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24075-x","article-title":"GADD45A and CDKN1A are involved in apoptosis and cell cycle modulatory effects of viscumTT with further inactivation of the STAT3 pathway.","volume":"8","author":"Kleinsimon","year":"2018","journal-title":"Sci. Rep."},{"key":"B18","doi-asserted-by":"publisher","first-page":"G772","DOI":"10.1152\/ajpgi.00125.2019","article-title":"Pregnancy facilitates maternal liver regeneration after partial hepatectomy.","volume":"318","author":"Lee","year":"2020","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"347","DOI":"10.3892\/ijmm.2017.2854","article-title":"The role of lncRNA MALAT1 in the regulation of hepatocyte proliferation during liver regeneration.","volume":"39","author":"Li","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1096\/fj.201800667R","article-title":"Dual regulatory role of CCNA2 in modulating CDK6 and MET-mediated cell-cycle pathway and EMT progression is blocked by miR-381-3p in bladder cancer.","volume":"33","author":"Li","year":"2019","journal-title":"FASEB J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.bbrc.2019.12.058","article-title":"Depletion of UBE2C reduces ovarian cancer malignancy and reverses cisplatin resistance via downregulating CDK1.","volume":"523","author":"Li","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B22","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1111\/wrr.12703","article-title":"Liver-specific Sirtuin6 ablation impairs liver regeneration after 2\/3 partial hepatectomy.","volume":"27","author":"Liu","year":"","journal-title":"Wound Repair Regen."},{"key":"B23","doi-asserted-by":"publisher","first-page":"9280","DOI":"10.12659\/MSM.918620","article-title":"Identification and Integrated Analysis of Key Biomarkers for Diagnosis and Prognosis of Non-Small Cell Lung Cancer.","volume":"25","author":"Liu","year":"","journal-title":"Med. Sci. Monit."},{"key":"B24","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1158\/1541-7786.MCR-19-0561","article-title":"UBE2C Is Upregulated by Estrogen and Promotes Epithelial-Mesenchymal Transition via p53 in Endometrial Cancer.","volume":"18","author":"Liu","year":"2020","journal-title":"Mol. Cancer Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1994","DOI":"10.1016\/j.celrep.2018.01.086","article-title":"LKB1 as a Gatekeeper of Hepatocyte Proliferation and Genomic Integrity during Liver Regeneration.","volume":"22","author":"Maillet","year":"2018","journal-title":"Cell Rep."},{"key":"B26","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1002\/jcp.21172","article-title":"Liver regeneration.","volume":"213","author":"Michalopoulos","year":"2007","journal-title":"J. Cell Physiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1177\/0023677215572000","article-title":"Partial hepatectomy in mice.","volume":"1","author":"Nevzorova","year":"2015","journal-title":"Lab. Anim."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8794013","article-title":"Screening and Bioinformatics Analysis of IgA Nephropathy Gene Based on GEO Databases.","volume":"2019","author":"Qian","year":"2019","journal-title":"Biomed. Res. Int."},{"key":"B29","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1002\/cncr.31837","article-title":"Aneuploid acute myeloid leukemia exhibits a signature of genomic alterations in the cell cycle and protein degradation machinery.","volume":"125","author":"Simonetti","year":"2019","journal-title":"Cancer"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118821","article-title":"hUCB-MSC derived exosomal miR-124 promotes rat liver regeneration after partial hepatectomy via downregulating Foxg1.","volume":"265","author":"Song","year":"2021","journal-title":"Life Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/B978-0-12-391498-9.00003-6","article-title":"Control of growth during regeneration.","volume":"108","author":"Sun","year":"2014","journal-title":"Curr. Top Dev. Biol."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/4256352","article-title":"Liver Regeneration: Analysis of the Main Relevant Signaling Molecules.","volume":"2017","author":"Tao","year":"2017","journal-title":"Mediators Inflamm."},{"key":"B33","doi-asserted-by":"publisher","first-page":"3625","DOI":"10.1016\/j.celrep.2018.03.010","article-title":"Single-Cell Deconvolution of Fibroblast Heterogeneity in Mouse Pulmonary Fibrosis.","volume":"22","author":"Xie","year":"2018","journal-title":"Cell Rep."},{"key":"B34","doi-asserted-by":"publisher","first-page":"G87","DOI":"10.1152\/ajpgi.00380.2019","article-title":"Inhibition of LXR signaling by SULT2B1b promotes liver regeneration after partial hepatectomy in mouse models of nonalcoholic fatty liver disease.","volume":"319","author":"Zhang","year":"2020","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.670706\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T04:59:16Z","timestamp":1624424356000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.670706\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,23]]},"references-count":34,"alternative-id":["10.3389\/fgene.2021.670706"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2021.670706","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,23]]},"article-number":"670706"}}