{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T13:24:25Z","timestamp":1780579465725,"version":"3.54.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T00:00:00Z","timestamp":1744416000000},"content-version":"vor","delay-in-days":70,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470693"],"award-info":[{"award-number":["82470693"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Gallbladder cancer (GBC) ranks as the most common malignant tumor of the biliary tract, which has been characterized by late diagnosis, low excisional rate, and poor prognosis. Recent studies exploring the roles of malignant progression-associated genes in GBC remain limited. Our study aims to identify significant hub genes involved in its pathogenesis, which may serve as novel potential therapeutic targets for GBC. Here, we employed RNA-seq analysis to identify differentially expressed genes (DEGs) of seven GBC samples and five matched adjacent samples. After screening the DEGs in clinical sequencing data and GSE139682, we further obtained 549 genes with consistent expression trends in two datasets, including 155 upregulated and 394 downregulated genes. Gene Ontology (GO) enrichment analysis revealed that these genes were significantly enriched in extracellular matrix (ECM)-related processes, such as organization, structure, and composition, which hint to us that remodeling of ECM may be the main driving factor for the malignant progression of GBC. In addition, we screened 17 candidate hub genes through protein-protein interaction (PPI) network analysis and Cytoscape, subsequent GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the remodeled ECM mainly functions by affecting cell division. Moreover, we found that NEK2 and NUF2 were overexpressed in GBC tumor tissues and validated their function in the pro-proliferation of GBC cells. Our results highlight that NEK2 and NUF2 may be hub genes promoting the malignant progression of GBC and are expected to be reliable new therapeutic targets for GBC.<\/jats:p>","DOI":"10.1093\/carcin\/bgaf019","type":"journal-article","created":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T21:06:44Z","timestamp":1744492004000},"source":"Crossref","is-referenced-by-count":3,"title":["NUF2 and NEK2 promote malignant progression of gallbladder cancer by remodeling the extracellular matrix"],"prefix":"10.1093","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9261-4910","authenticated-orcid":false,"given":"Ming","family":"Gao","sequence":"first","affiliation":[{"name":"Hepatobiliary and Pancreatic Surgery and Liver Transplantation Center, First Hospital of Shanxi Medical University , No. 85 Jiefang South Road, Taiyuan, Shanxi 030001 ,","place":["China"]},{"name":"Faculty of Graduate Studies, Shanxi Medical University , No. 56 Xinjian South Road, Taiyuan, Shanxi 030001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Ye","sequence":"additional","affiliation":[{"name":"Faculty of Graduate Studies, Shanxi Medical University , No. 56 Xinjian South Road, Taiyuan, Shanxi 030001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Faculty of Graduate Studies, Shanxi Medical University , No. 56 Xinjian South Road, Taiyuan, Shanxi 030001 ,","place":["China"]},{"name":"Key Laboratory of Cellular Physiology of the Ministry of Education (Shanxi Medical University), Translational Medicine Research Center, Department of Pathology, Shanxi Medical University , No. 56 Xinjian South Road, Taiyuan, Shanxi 030001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yarong","family":"Guo","sequence":"additional","affiliation":[{"name":"Oncology Department, Shanxi Bethune Hospital , No. 99 Longcheng Street, Taiyuan, Shanxi 030032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Xu","sequence":"additional","affiliation":[{"name":"Hepatobiliary and Pancreatic Surgery and Liver Transplantation Center, First Hospital of Shanxi Medical University , No. 85 Jiefang South Road, Taiyuan, Shanxi 030001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,4,12]]},"reference":[{"key":"2025060501364551500_CIT0001","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"2025060501364551500_CIT0002","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41572-022-00398-y","article-title":"Gallbladder 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