Essential role of the histone lysine demethylase KDM4A in the biology of malignant pleural mesothelioma (MPM).

ABSTRACT:

Background

Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with a dismal prognosis. There is increasing interest in targeting chromatin regulatory pathways in difficult-to-treat cancers. In preliminary studies, we found that KDM4A (lysine-specific histone demethylase 4) was overexpressed in MPM.

Methods

KDM4A protein expression was determined by immunohistochemistry or immunoblotting. Functional inhibition of KDM4A by targeted knockdown and small molecule drugs was correlated to cell growth using cell lines and a xenograft mouse model. Gene expression profiling was performed to identify KDM4A-dependent signature pathways.

Results

Levels of KDM4A were found to be significantly elevated in MPM patients compared to normal mesothelial tissue. Inhibiting

SUBMITTER: Lapidot M 

PROVIDER: S-EPMC8368004 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature