{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:03:03Z","timestamp":1785416583683,"version":"3.56.0"},"reference-count":45,"publisher":"IMR Press","issue":"7","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jinan Municipal Health Commission Science and Technology Program","award":["2023-1-5"],"award-info":[{"award-number":["2023-1-5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background:Kidney renal clear cell carcinoma (KIRC) is the most common subtype of renal cell carcinoma, accounting for 75\u201380% of cases. Although Prohibitin 1 (PHB1) has been implicated in tumorigenesis, its role in KIRC remains unclear. This study aimed to investigate the expression, function, and underlying mechanisms of PHB1 in KIRC.Methods:PHB1 expression and clinical relevance were analyzed using the Cancer Genome Atlas database (TCGA), Gene Expression Omnibus database (GEO), and TIMER3.0 datasets. Single-cell RNA sequencing (scRNA-seq) data from 19 KIRC patients and normal kidney samples were used to assess cell-type-specific expression. Functional experiments, including CCK-8, EdU incorporation, colony formation, and Transwell assays, were performed to evaluate the effects of PHB1 on cell proliferation, migration, and invasion. A xenograft model was used to evaluate the effects of PHB1 in vivo. Western blotting and correlation analyses were conducted to assess the potential regulatory interplay between VHL, SKP2, PHB1, and p53.Results:PHB1 was significantly downregulated in KIRC tissues. Single-cell analysis showed reduced PHB1 expression in tumor-derived epithelial cells, fibroblasts, endothelial cells, and immune cells. Lower PHB1 levels were associated with poorer overall survival. PHB1 overexpression inhibited proliferation and migration, whereas knockdown promoted these effects. In vivo, PHB1 overexpression reduced tumor growth. Moreover, VHL knockout altered the protein levels of SKP2 and PHB1. Cellular manipulation of PHB1 moderately altered endogenous p53 protein expression. Based on TCGA data analysis, PHB1 expression showed a positive correlation with VHL and a negative correlation with SKP2.Conclusions:Collectively, PHB1 acts as a potential tumor suppressor in KIRC. Its expression pattern is associated with the VHL-SKP2 signaling axis, and the tumor-suppressive effects of PHB1 may be partially associated with the modulation of p53 expression. These findings suggest that PHB1 has the potential to serve as a reliable biomarker and therapeutic candidate for KIRC treatment.<\/jats:p>","DOI":"10.31083\/fbl53057","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:17:49Z","timestamp":1785413869000},"source":"Crossref","is-referenced-by-count":0,"title":["Downregulation of PHB1 due to Loss of VHL Protein Expression Promotes the Malignancy Progression of Kidney Renal Clear Cell Carcinoma"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2590-1849","authenticated-orcid":true,"given":"Chenbin","family":"Cao","sequence":"first","affiliation":[{"name":"School of Medical Laboratory, Shandong Second Medical University, 261053 Weifang, Shandong, China"},{"name":"Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, 250013 Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2688-7071","authenticated-orcid":true,"given":"He","family":"Qi","sequence":"additional","affiliation":[{"name":"School of Medical Laboratory, Shandong Second Medical University, 261053 Weifang, Shandong, China"},{"name":"Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, 250013 Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9620-981X","authenticated-orcid":true,"given":"Lu","family":"Xiang","sequence":"additional","affiliation":[{"name":"Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, 250013 Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9027-1290","authenticated-orcid":true,"given":"Wenshuai","family":"Zhu","sequence":"additional","affiliation":[{"name":"Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, 250013 Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9507-7312","authenticated-orcid":true,"given":"Yuxuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Research Center of Basic Medicine, Jinan Central Hospital, Shandong University, 250013 Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0279-8354","authenticated-orcid":true,"given":"Xiaoli","family":"Ma","sequence":"additional","affiliation":[{"name":"Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, 250013 Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunshan","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, 250013 Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0670-1604","authenticated-orcid":true,"given":"Yanfei","family":"Jia","sequence":"additional","affiliation":[{"name":"School of Medical Laboratory, Shandong Second Medical University, 261053 Weifang, Shandong, China"},{"name":"Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, 250013 Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0294-1914","authenticated-orcid":true,"given":"Yuanxin","family":"Xing","sequence":"additional","affiliation":[{"name":"Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, 250013 Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L, Schmidinger M, et al. 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Journal of Experimental & Clinical Cancer Research : CR. 2023; 42: 128.","DOI":"10.1186\/s13046-023-02695-0"},{"key":"ref14","unstructured":"Wu TF, Wu H, Wang YW, Chang TY, Chan SH, Lin YP, et al. Prohibitin in the pathogenesis of transitional cell bladder cancer. Anticancer Research. 2007; 27: 895\u2013900."},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Jiang L, Dong P, Zhang Z, Li C, Li Y, Liao Y, et al. Akt phosphorylates Prohibitin 1 to mediate its mitochondrial localization and promote proliferation of bladder cancer cells. Cell Death & Disease. 2015; 6: e1660.","DOI":"10.1038\/cddis.2015.40"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Guo F, Hiroshima K, Wu D, Satoh M, Abulazi M, Yoshino I, et al. Prohibitin in squamous cell carcinoma of the lung: its expression and possible clinical significance. Human Pathology. 2012; 43: 1282\u20131288.","DOI":"10.1016\/j.humpath.2011.10.006"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Javid H, Hashemy I, Shahidsales S, Mohammadian Roshan N, Kianoosh T, Zahedi Avval F. Tissue Expression of Prohibition-I and It's Relationship With Prognostic Factors in Breast Cancer. Iranian Journal of Pathology. 2018; 13: 237\u2013244.","DOI":"10.30699\/ijp.13.2.237"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"El-Etreby NM, Ghazy AA, Rashad R. Prohibitin: targeting peptide coupled to ovarian cancer, luteinization and TGF-\u03b2 pathways. Journal of Ovarian Research. 2017; 10: 28.","DOI":"10.1186\/s13048-017-0325-4"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Gregory-Bass RC, Olatinwo M, Xu W, Matthews R, Stiles JK, Thomas K, et al. Prohibitin silencing reverses stabilization of mitochondrial integrity and chemoresistance in ovarian cancer cells by increasing their sensitivity to apoptosis. 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