{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T20:20:47Z","timestamp":1772828447565,"version":"3.50.1"},"reference-count":76,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/objectives: Nucleolin is a major component of the nucleolus and is involved in various aspects of ribosome biogenesis. However, it is also implicated in non-nucleolar functions such as cell cycle regulation and proliferation, linking it to various pathologic processes. The aim of this study was to use differential gene expression analysis and Weighted Gene Co-expression Network analysis (WGCNA) to identify nucleolin-related regulatory pathways and possible key genes as novel therapeutic targets for cancer, viral infections and other diseases. Methods: We used two different siRNAs to downregulate the expression of nucleolin in a human hepatoblastoma (HepG2) cell line. We carried out RNA-sequencing (RNA-Seq), performed enrichment analysis of the pathways of the differentially expressed genes (DEGs) and identified protein\u2013protein interaction (PPI) networks. Results: Both siRNAs showed high knockdown efficiency in HepG2 cells, resulting in the disruption of the nucleolar architecture and the downregulation of rRNA gene expression, both downstream hallmarks of a loss of nucleolin function. RNA-Seq identified 44 robust DEGs in both siRNA cell models. The enrichment analysis of the pathways of the downregulated genes confirmed the essential role of nucleolin in DNA replication and cell cycle processes. In addition, we identified seven hub genes linked to NCL: MCM6, MCM3, FEN1, MYBL2, MSH6, CDC6 and RBM14; all are known to be implicated in DNA replication, cell cycle progression and oncogenesis. Conclusions: Our findings demonstrate the functional consequences of nucleolin depletion in HepG2 and confirm the importance of nucleolin in DNA replication and cell cycle processes. These data will further enhance our understanding of the molecular and pathologic mechanisms of nucleolin and provide new therapeutic perspectives in disease.<\/jats:p>","DOI":"10.3390\/genes15121514","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T04:02:18Z","timestamp":1732593738000},"page":"1514","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["RNA Sequencing and Weighted Gene Co-Expression Network Analysis Highlight DNA Replication and Key Genes in Nucleolin-Depleted Hepatoblastoma Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4438-6043","authenticated-orcid":false,"given":"Hannes","family":"Steinkellner","sequence":"first","affiliation":[{"name":"Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4995-7351","authenticated-orcid":false,"given":"Silvia","family":"Madritsch","sequence":"additional","affiliation":[{"name":"Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara","family":"Kluge","sequence":"additional","affiliation":[{"name":"Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Seipel","sequence":"additional","affiliation":[{"name":"Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1053-4033","authenticated-orcid":false,"given":"Victoria","family":"Sarne","sequence":"additional","affiliation":[{"name":"Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Vienna Doctoral School of Pharmaceutical, Nutritional and Sport Sciences (PhaNuSpo), University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8490-9630","authenticated-orcid":false,"given":"Anna","family":"Huber","sequence":"additional","affiliation":[{"name":"Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Vienna Doctoral School of Pharmaceutical, Nutritional and Sport Sciences (PhaNuSpo), University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Schosserer","sequence":"additional","affiliation":[{"name":"Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6701-4130","authenticated-orcid":false,"given":"Raimund","family":"Oberle","sequence":"additional","affiliation":[{"name":"Center for Pathobiochemistry and Genetics, Institute of Medical Chemistry and Pathobiochemistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6552-7183","authenticated-orcid":false,"given":"Winfried","family":"Neuhaus","sequence":"additional","affiliation":[{"name":"Competence Unit Molecular Diagnostics, Center Health and Bioresources, AIT-Austrian Institute of Technology GmbH, 1210 Vienna, Austria"},{"name":"Department of Medicine, Faculty of Medicine and Dentistry, Danube Private University, 3500 Krems an der Donau, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander V.","family":"Beribisky","sequence":"additional","affiliation":[{"name":"Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9466-6441","authenticated-orcid":false,"given":"Franco","family":"Laccone","sequence":"additional","affiliation":[{"name":"Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0014-4827(81)90041-0","article-title":"Localization of phosphoprotein C23 to nucleolar structures and to the nucleolus organizer regions","volume":"136","author":"Lischwe","year":"1981","journal-title":"Exp. 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