YAP inhibits the sensitivity of BRAF V600E mutant CRC cells to MAPK (RAS→RAF→MEK→ERK) pathway inhibitors. (A,B) MTS method was used to detect the proliferation activity of cells. Knockdown of YAP increased the sensitivity of RKO and HT29 CRC cells to vemurafenib, trametinib, C+V, and C+V+T, but had little effect on the cells treated with PBS. (C) Knockdown of YAP had no significant effect on the sensitivity of cytotoxic chemotherapeutic drugs L-OHP and SN38. (D) Transcriptomics tests the differential gene expression of HT29 cells that normally express wild-type YAP and YAP knockdown HT29 cells. The results show that the differential expression of multiple genes related to the cell cycle and FoxO signaling pathway. (E,F) CDK6 (cycle correlation) and SGK1 (FoxO pathway) genes are differentially expressed in these two pathways. Therefore, CHIP experiment was further performed to confirm the transcriptional regulation of YAP. *, P<0.1. **P<0.05, ***P<0.01. CRC, colorectal cancer; YAP, yes-associated protein.