To further clarify the downstream mechanism of circ-MTHFD1L maintaining gemcitabine resistance, we divided the pancreatic cancer patients in The Cancer Genome Atlas (TCGA) database into two groups with high RPN6 expression and low RPN6 expression, and then performed Gene set enrichment analysis (GSEA), the results show that the high expression of RPN6 is highly correlated with cell cycle, DNA double-strand break repair and homologous recombination (Fig. 6A-C). Here, MTHFD1L is linked to familial pancreatic carcinoma.