Human gastric cancer cell lines AGS PICH/ATF4 ChIP-seq Raw sequence reads
PICH was identified as a potential predictor of 5-FU chemosensitivity and was discovered an uncovered transcriptional function distinct from its role in chromosome separation. PICH forms a transcriptional machinery with RNA polymerase II (Pol II) and ATF4 at the Cyclin A1 promoter in an ATPase-dependent manner to promote Cyclin A1 transcription and accelerate S phase progression. Overexpressed PICH impairs 5-FU chemosensitivity in human organoids and patient-derived xenografts and is negatively correlated with survival in postoperative patients receiving 5-FU chemotherapy. These findings reveal that ATPase-dependent PICH facilitates Cyclin A1 transcription with Pol II and ATF4 to drive 5-FU chemoresistance, which provides a potential predictor of 5-FU chemosensitivity for postoperative GC patients and prompts further study into the transcriptional function of PICH.