Cullin 4B Ubiquitin Ligase Is Important for Cell Survival and Regulates TGF-β1 Expression in Pleural Mesothelioma.

ABSTRACT: We previously demonstrated that cullin 4B (CUL4B) upregulation was associated with worse outcomes of pleural mesothelioma (PM) patients, while the overexpression of its paralog CUL4A was not associated with clinical outcomes. Here, we aimed to identify the distinct roles of CUL4B and CUL4A in PM using an siRNA approach in PM cell lines (ACC Meso-1 and Mero82) and primary culture. The knockdown of CUL4B and CUL4A resulted in significantly reduced colony formation, increased cell death, and delayed cell proliferation. Furthermore, similar to the effect of CUL4A knockdown, downregulation of CUL4B led to reduced expression of Hippo pathway genes including YAP1, CTGF, and survivin. Interestingly, CUL4B and not CUL4A knockdown reduced TGF-β1 and MMP2 expression, suggesting a unique association o

SUBMITTER: Kreienbuhl J 

PROVIDER: S-EPMC10487616 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature