Dataset Information

SPOP promotes tumorigenesis by acting as a key regulatory hub in kidney cancer.

ABSTRACT: Hypoxic stress and hypoxia-inducible factors (HIFs) play important roles in a wide range of tumors. We demonstrate that SPOP, which encodes an E3 ubiquitin ligase component, is a direct transcriptional target of HIFs in clear cell renal cell carcinoma (ccRCC). Furthermore, hypoxia results in cytoplasmic accumulation of SPOP, which is sufficient to induce tumorigenesis. This tumorigenic activity occurs through the ubiquitination and degradation of multiple regulators of cellular proliferation and apoptosis, including the tumor suppressor PTEN, ERK phosphatases, the proapoptotic molecule Daxx, and the Hedgehog pathway transcription factor Gli2. Knockdown of SPOP specifically kills ccRCC cells, indicating that it may be a promising therapeutic target. Collectively, our results indicate that SPOP serves as a regulatory hub to promote ccRCC tumorigenesis.

SUBMITTER: Li G

PROVIDER: S-EPMC4443692 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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SPOP promotes tumorigenesis by acting as a key regulatory hub in kidney cancer.

Li Guoqiang G Ci Weimin W Karmakar Subhradip S Chen Ke K Dhar Ruby R Fan Zhixiang Z Guo Zhongqiang Z Zhang Jing J Ke Yuwen Y Wang Lu L Zhuang Min M Hu Shengdi S Li Xuesong X Zhou Liqun L Li Xianghong X Calabrese Matthew F MF Watson Edmond R ER Prasad Sandip M SM Rinker-Schaeffer Carrie C Eggener Scott E SE Stricker Thomas T Tian Yong Y Schulman Brenda A BA Liu Jiang J White Kevin P KP

Cancer cell 20140320 4

Hypoxic stress and hypoxia-inducible factors (HIFs) play important roles in a wide range of tumors. We demonstrate that SPOP, which encodes an E3 ubiquitin ligase component, is a direct transcriptional target of HIFs in clear cell renal cell carcinoma (ccRCC). Furthermore, hypoxia results in cytoplasmic accumulation of SPOP, which is sufficient to induce tumorigenesis. This tumorigenic activity occurs through the ubiquitination and degradation of multiple regulators of cellular proliferation and ...[more]

PMID: 24656772

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Project description:IntroductionProstate cancer (PCa) is one of the most common malignant tumors of the male urogenital system; however, the underlying mechanisms remain largely unclear. This study integrated two cohort profile datasets to elucidate the potential hub genes and mechanisms in PCa.Methods and resultsGene expression profiles GSE55945 and GSE6919 were filtered from the Gene Expression Omnibus (GEO) database to obtain 134 differentially expressed genes (DEGs) (14 upregulated and 120 downregulated) in PCa. Gene Ontology and pathway enrichment were performed using the Database for Annotation, Visualization, and Integrated Discovery, showing that these DEGs were mainly involved in biological functions such as cell adhesion, extracellular matrix, migration, focal adhesion, and vascular smooth muscle contraction. The STRING database and Cytoscape tools were used to analyze protein-protein interactions and identify 15 hub candidate genes. Violin plot, boxplot, and prognostic curve analyses were performed using Gene Expression Profiling Interactive Analysis, which identified seven hub genes, including upregulated expressed SPP1 and downregulated expressed MYLK, MYL9, MYH11, CALD1, ACTA2, and CNN1 in PCa compared with normal tissue. Correlation analysis was performed using the OmicStudio tools, which showed that these hub genes were moderately to strongly correlated with each other. Finally, quantitative reverse transcription PCR and western blotting were performed to validate the hub genes, showing that the abnormal expression of the seven hub genes in PCa was consistent with the analysis results of the GEO database.DiscussionTaken together, MYLK, MYL9, MYH11, CALD1, ACTA2, SPP1, and CNN1 are hub genes significantly associated with PCa occurrence. These genes are abnormally expressed, leading to the formation, proliferation, invasion, and migration of PCa cells and promoting tumor neovascularization. These genes may serve as potential biomarkers and therapeutic targets in patients with PCa.

Dataset Information

SPOP promotes tumorigenesis by acting as a key regulatory hub in kidney cancer.

Publications

SPOP promotes tumorigenesis by acting as a key regulatory hub in kidney cancer.

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