DNA Methylation Mediates EMT Gene Expression in Human Pancreatic Ductal Adenocarcinoma Cell Lines
Year: 2022
Type: article
Abstract: Due to abundant stroma and extracellular matrix, accompanied by lack of vascularization, pancreatic ductal adenocarcinoma (PDAC) is characterized by severe hypoxia. Epigenetic regulation is likely one of the mechanisms driving hypoxia-induced epithelial-to-mesenchymal transition (EMT), responsible for PDAC aggressiveness and dismal prognosis. To verify the role of DNA methylation in this process, we assessed gene expression and DNA methylation changes in four PDAC cell lines. BxPC-3, MIA PaCa-2, PANC-1, and SU.86.86 cells were exposed to conditioned media containing cytokines and inflammatory molecules in normoxic and hypoxic (1% O2) conditions for 2 and 6 days. Cancer Inflammation and Immunity Crosstalk and Human Epithelial to Mesenchymal Transition RT² Profiler PCR Arrays were used to identify top deregulated inflammatory and EMT-related genes. Their mRNA expression and DNA methylation were quantified by qRT-PCR and pyrosequencing. BxPC-3 and SU.86.86 cell lines were the most sensitive to hypoxia and inflammation. Although the methylation of gene promoters correlated with gene expression negatively, it was not significantly influenced by experimental conditions. However, DNA methyltransferase inhibitor decitabine efficiently decreased DNA methylation up to 53% and reactivated all silenced genes. These results confirm the role of DNA methylation in EMT-related gene regulation and uncover possible new targets involved in PDAC progression.
DOI: 10.3390/ijms23042117
Institutions: Slovak Academy of Sciences, Cancer Research Institute of the Slovak Academy of Sciences, Biomedical Research Center of the Slovak Academy of Sciences, Institute of Virology of the Slovak Academy of Sciences, Instituto Ramón y Cajal de Investigación Sanitaria, Centro de Investigación Biomédica en Red de Cáncer, Slovak Medical University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,408
Awards: Samovražedná génová terapia sprostredkovaná exozómami z mezenchýmových stromálnych a pankreatických nádorových buniek v liečbe duktálneho adenokarcinómu pankreasu, G3463486190, G4143398449, Strategies to strengthen scientific excellence and innoVation capacIty for early diagnoSIs of gastrOintestinal caNcers, Štúdium dynamiky zápalom-indukovaných epigenetických zmien v procese epiteliálno-mezenchymálneho prechodu a ich úlohy v progresii duktálneho adenokarcinómu pankreasu, G6222010595, G7761450427, Cytokínové profilovanie v spojení s imunotargetingom karbonickej anhydrázy IX ako perspektívny nástroj v diagnostike a liečbe rakoviny pankreasu.
OpenAlex ID: W4213029009