Effects of SOX9 Downregulation on the Transcriptomic Landscape of Pancreatic Ductal Adenocarcinoma Cells

SOX9 is recognized as a crucial master regulator of gene transcription, playing a significant role in the developmental and differentiation processes of tissue and organ formation, particularly in the pancreas. Its overexpression has been associated with various tumors, including pancreatic cancer, and is often discussed as a potential prognostic marker. In this study, we conducted SOX9 knockdown in Colo375 and PANC-1 cell lines using RNA interference, followed by comprehensive transcriptome analysis of the transfected cells. We performed gene annotation and pathway analysis, as well as examined gene signatures related to survival and chemoresistance in pancreatic cancer within the transcriptomes of siSOX9 transfected cells. Notable differences were observed between the transcriptomes of SOX9 knockdown and control cells, including the activation of signaling pathways, differentiation processes, transcription, and methylation, alongside a reduction in the expression of genes associated with the cell cycle and apoptosis. The analysis revealed alterations in transcription factors, differentially expressed genes, oncogenes, tumor suppressor genes, genes related to epithelial-mesenchymal transition, drug resistance, and those included in prognostic signatures for pancreatic cancer in the SOX9 knockdown cells. The findings suggest that SOX9 may not serve as a reliable prognostic marker in pancreatic cancer.