MRP4 overexpression induces an altered epigenetic and transcriptional program that contributes to tumor progression in pancreatic cancer.

SAMANTA N GANCEDO; ANA SAHORES; NATALIA GOMEZ; MAXIMILIANO DE SOUSA SERRO; AGUSTIN YANNEF; CARLOS DAVIO; BETINA GONZALEZ

Congreso; Reunion Anual de Sociedades de Biociencia 2022; 2022

The multidrug resistance-associated protein 4 (MRP4/ABCC4) is highly expressed in pancreatic ductal adenocarcinoma (PDAC), and its overexpression is linked to increased tumor proliferation and metastatic capacity. The aim of this study was to determine how MRP4 overexpression collaborates in the establishment of malignant epigenetic and transcriptional programs that sustain tumor progression. For this, we performed RNAseq studies of BxPC3 cells stable transfected with a ABCC4-expressing (-MRP4) plasmid or an empty vector (-mock) in two different environmental growing contexts: cell culture or tumor xenografts obtained from subcutaneous inoculation of these cells in NSG mice. Transcriptome analysis (FDR0.5) showed 2,043 differentially expressed genes (DEGs) between -MRP4 and -mock cells growing in culture, and 4,234 DEGs when comparing -MRP4 and -mock xenograft samples. Interestingly, we found common deregulated pathways shared by culture and xenograft samples related to a proliferative and metastatic signature in PDAC cells. In addition, xenograft samples showed specific pathways related to epigenetic changes, including histone acetylation and methylation terms (FDR