Downregulation of WDR20 due to loss of 14q is involved in the malignant transformation of clear cell renal cell carcinoma

Cancer Science
Mika TakahashiMasatsugu Moriyama

Abstract

Previously, we reported that genomic loss of 14q occurs more frequently in high-grade than in low-grade clear cell renal cell carcinomas (ccRCCs), and has a significant impact on the levels of expression of genes located in this region, suggesting that such genes may be involved in the malignant transformation of ccRCCs. Here, we found that six of the genes located in the minimal common region of 14q loss were significantly downregulated in high-grade ccRCCs due to copy number loss. Using a dataset from The Cancer Genome Atlas Research Network, we found that downregulation of one of these six genes, WDR20, was significantly associated with poorer outcome in patients with ccRCC, suggesting that WDR20 downregulation may be involved in the malignant transformation of ccRCCs. In functional assays, exogenous WDR20 significantly inhibited the growth of RCC cell lines and induced apoptosis. Interestingly, the phosphorylation levels of ERK and protein kinase B/AKT, which reportedly contribute to the malignant phenotype of RCC cells, were clearly reduced by exogenous expression of WDR20. Thus, our data suggest that downregulation of WDR20 due to 14q loss may be involved in the malignant transformation of ccRCCs, in part through activati...Continue Reading

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Citations

Oct 28, 2018·Nature Communications·Daniele RamazzottiArend Sidow
Feb 1, 2020·Pharmacology & Therapeutics·Elena MariottoSanja Aveic
Feb 27, 2021·Computational Biology and Chemistry·Feng LiZhiyu Wang
May 27, 2021·The Journal of International Medical Research·Jing-Hang MaZhen Feng
Nov 16, 2021·Molecular Medicine Reports·Hua-Chuan Zheng, Hua-Mao Jiang

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Methods Mentioned

BETA
ELISA
PCR
deubiquitination
transfection

Software Mentioned

cBioPortal

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