IRS1 and cholangiocarcinoma: Moreover, the RNA sequencing results demonstrated the absolute fold changes of cell proliferation, and DNA replication-related genes were down-regulated in the IRS1 knockdown CCA cells (siIRS1) compared to the vehicle control cells (scramble), as shown in Figure 5C. The pathways related to cell proliferation and DNA replication were also verified using the Reactome database (Figure 5D).