Wild-type p53 regulates OTOP2 transcription through DNA loop alteration of the promoter in colorectal cancer.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide and remains a major public health issue. Therefore, further investigation is required to delineate the cellular and molecular mechanisms underlying colorectal tumorigenesis. Using CRC data taken from The Cancer Genome Atlas, we determined that the expression of otopetrin 2 (OTOP2) is highly correlated with malignancy grade and rate of patient survival. Here, we report that OTOP2 is down-regulated in cancerous tissues and that elevated OTOP2 effectively suppresses tumor proliferation in vitro. We demonstrate that wild-type p53 (wtp53), but not mutant p53 (mtp53), can regulate the transcription of otop2 in CRC cells. Subsequently, we investigate the chromatin architecture of the otop2 promoter, whereby we discover alterations in p53-dependent DNA loop organization and CCCTC-binding factor (CTCF) binding between cells with wtp53 and mtp53. In conclusion, our study promotes an in-depth understanding of tumorigenesis, which may also lead to the development of therapeutic applications targeting human malignancy.