BMI Expression is Required for Pancreatic Cancer Progression

ABSTRACT: Pancreatic cancer is one of the deadliest human malignancies, with a survival rate less than 10%. Traditional modes of therapy have proven ineffective in the treatment of pancreatic cancer, highlighting the need to further understand the basic biology of the disease in order to identify new treatment modalities. Previously, our group showed that the epigenetic regulator Bmi1 is required for the initiation of pancreatic cancer in mice. In murine models of PDAC, mice lacking pancreatic Bmi1 expression do not develop precancerous lesions, despite oncogene expression. In this work, we sought to determine the role of Bmi1 in later stages of pancreatic tumor development. Using a CRISPR/Cas9 strategy, we deleted Bmi1 in primary human pancreatic caner cells and created clonal lines. When used in a subcutaenous tumor growth assay, those cells lacking BMI1 expression formed tumors that grew significantly smaller than controls. To query the mechanism of BMI1 action in pancreatic cancer growth, we used RNA sequencing to compare those pancreatic cancer cells with and without BMI1 expressed. This revealed that Bmi1 controls the gene expression of glycolysis and cell proliferation pathways, likely the reason for its requirement in pancreatic tumor growth. Overall, we found that Bmi1 is required in pancreatic tumor progression, and that it controls gene expression in both glycolysis and cell proliferation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE149981 | GEO | 2023/06/30

REPOSITORIES: GEO