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Series GSE186717 Query DataSets for GSE186717
Status Public on Jul 27, 2022
Title USP13 Promotes Deubiquitination of ZHX2 and Tumorigenesis in Kidney Cancer
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Clear cell renal cell carcinoma (ccRCC) is characterized by loss of tumor suppressor Von Hippel Lindau (VHL) function. VHL is the component of E3 ligase complex that promotes the ubiquitination and degradation of hypoxia inducible factor alpha (including HIF1alpha and HIF2alpha) and Zinc Fingers And Homeoboxes 2 (ZHX2). Our recent research showed that ZHX2 contributed to ccRCC tumorigenesis in a HIF independent manner. However, it remains unknown whether ZHX2 can be regulated through deubiquitination. Here we performed a deubiquitinase (DUB) cDNA library binding screen and identified USP13 as a novel DUB that bound ZHX2 and promoted ZHX2 deubiquitination. As a result, USP13 promoted ZHX2 protein stability in an enzymatically dependent manner and depletion of USP13 led to ZHX2 downregulation in ccRCC. Functionally, USP13 depletion led to decreased cell proliferation measured by 2-D colony formation and 3-D anchorage independent growth. USP was a critical effector on maintaining kidney tumorigenesis in an orthotopic xenograft model and its depletion led to both decreased primary kidney tumorigenesis and spontaneous lung metastasis. Our results suggest that USP13 is a potential new therapeutic target in ccRCC.
 
Overall design RNA-seq in 786-O cells after knockdown of ZHX2 or USP13 with two different shRNAs
 
Contributor(s) Xie H, Zhou J, Xu Y, Liu X, Simon JM, Hepperla AJ, Liao C, Baldwin AS, Gong K, Zhang Q
Citation(s) 36037364
Submission date Oct 27, 2021
Last update date Sep 05, 2022
Contact name Jeremy M Simon
E-mail(s) jeremy_simon@med.unc.edu
Phone (919) 966-4050
Organization name University of North Carolina at Chapel Hill
Department Neuroscience
Street address 7018A Mary Ellen Jones Building
City Chapel Hill
State/province NC
ZIP/Postal code 27599
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (18)
GSM5659358 786-O_USP13_sh50_Rep1
GSM5659359 786-O_USP13_sh50_Rep2
GSM5659360 786-O_USP13_sh50_Rep3
Relations
BioProject PRJNA775640
SRA SRP343502

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Supplementary file Size Download File type/resource
GSE186717_786-O_shZHX2_shUSP13_shAll_vs_shCtrl_DEGs_diff_0.05.xlsx 4.7 Mb (ftp)(http) XLSX
GSE186717_RAW.tar 14.1 Mb (http)(custom) TAR (of SF)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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