HUWE1 controls the development of non-small cell lung cancer through down-regulation of p53

Theranostics
Dong YangXudong Zhao

Abstract

Lung cancer is the most frequent cancer type and the leading cause of tumor-associated deaths worldwide. TP53 is an important tumor suppressor gene and is frequently inactivated in lung cancer. E3 ligases targeting p53, such as MDM2, are involved in the development of lung cancer. The E3 ligase HUWE1, which targets many tumor-associated proteins including p53, has been reported to be highly expressed in lung cancer; however, its role in lung tumorigenesis is unclear. Methods: The expression of HUWE1 and p53 in lung cancer cells was modulated and the phenotypes were assessed by performing soft agar colony forming assays, cell cycle analysis, BrdU incorporation assays, and xenograft tumor growth assays. The effect on tumorigenesis in genetically-engineered mice was also analyzed. The mechanism through which HUWE1 sustained lung cancer cell malignancy was confirmed by western blotting. HUWE1 expression in clinical lung cancer was identified by immunohistochemistry and validated by analyzing lung adenocarcinoma and lung squamous carcinoma samples from the Cancer Genome Atlas (TCGA) database. Finally, we assessed the association between HUWE1 expression and patient outcome using online survival analysis software including survival i...Continue Reading

Citations

Aug 9, 2018·Chembiochem : a European Journal of Chemical Biology·Dan ChenSonja Lorenz
May 28, 2019·Cells·Monica Vara-PerezPatrizia Agostinis
Sep 29, 2020·Journal of Translational Internal Medicine·Hao QianYingxian Sun
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Methods Mentioned

BETA
PCR
flow cytometry
co-immunoprecipitation
protein assay
electrophoresis
xenograft
ubiquitination
RNA-Seq

Software Mentioned

GraphPad Prism
Target Finder
pTomo

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