Open AccessWild‐type p53 regulates OTOP 2 transcription through DNA loop alteration of the promoter in colorectal cancer
Author(s) -
Qu Huajun,
Su Yi,
Yu Lianzhi,
Zhao Hongchao,
Xin Chunxia
Publication year - 2019
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12554
Subject(s) - carcinogenesis , ctcf , biology , colorectal cancer , transcription factor , cancer research , chromatin , malignancy , mutant , wild type , cancer , microbiology and biotechnology , dna , genetics , gene , enhancer
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 ( OTOP 2) is highly correlated with malignancy grade and rate of patient survival. Here, we report that OTOP 2 is down‐regulated in cancerous tissues and that elevated OTOP 2 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.