Deciphering of SOX9 Functions in Pancreatic Cancer Cells

SOX9 is widely regarded as a key master regulator of gene transcription, responsible for the development and differentiation programs within tissue and organogenesis, particularly in the pancreas. SOX9 overexpression has been observed in multiple tumor types, including pancreatic cancer, and is discussed as a prognostic marker. In order to gain a more profound understanding of the role of SOX9 in pancreatic cancer, we have performed SOX9 knockdown in the COLO357 and PANC-1 cells using RNA interference, followed by full-transcriptome analysis of the siRNA-transfected cells. The molecular pathway enrichment analysis between SOX9-specific siRNA-transfected cells and control cells reveals the activation of processes associated with cellular signaling, cell differentiation, transcription, and methylation, alongside the suppression of genes involved in various stages of the cell cycle and apoptosis, upon the SOX9 knockdown. Alterations of the expression of transcription factors, epithelial–mesenchymal transition markers, oncogenes, tumor suppressor genes, and drug resistance-related genes upon SOX9 knockdown in comparison of primary and metastatic pancreatic cancer cells are discovered. The expression levels of genes comprising prognostic signatures for pancreatic cancer were also evaluated following SOX9 knockdown. Additional studies are needed to assess the properties and prognostic significance of SOX9 in pancreatic cancer using other biological models.