4.7 Article

Regulation Network of Colorectal-Cancer-Specific Enhancers in the Progression of Colorectal Cancer

Journal

Publisher

MDPI
DOI: 10.3390/ijms22158337

Keywords

colorectal-cancer-specific enhancer; long-range interaction; Hi-C; HiChIP; TAD

Funding

  1. Fundamental Research Funds for the Central Universities, Nankai University [63201087]
  2. National Natural Science Foundation of China [81772687]

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The study revealed the regulatory network of colorectal-cancer-specific enhancers, which are associated with changes in over 50% of the topological associated domains (TADs) and interact with 152 genes that are significantly highly expressed in colorectal cancer cells.
Enhancers regulate multiple genes via higher-order chromatin structures, and they further affect cancer progression. Epigenetic changes in cancer cells activate several cancer-specific enhancers that are silenced in normal cells. These cancer-specific enhancers are potential therapeutic targets of cancer. However, the functions and regulation networks of colorectal-cancer-specific enhancers are still unknown. In this study, we profile colorectal-cancer-specific enhancers and reveal their regulation network through the analysis of HiChIP data that were derived from a colorectal cancer cell line and Hi-C and RNA-seq data that were derived from tissue samples by in silico analysis and in vitro experiments. Enhancer-promoter loops in colorectal cancer cells containing colorectal-cancer-specific enhancers are involved in more than 50% of the topological associated domains (TADs) changed in colorectal cancer cells compared to normal colon cells. In addition, colorectal-cancer-specific enhancers interact with 152 genes that are significantly and highly expressed in colorectal cancer cells. These colorectal-cancer-specific enhancer target genes include ITGB4, RECQL4, MSLN, and GDF15. We propose that the regulation network of colorectal-cancer-specific enhancers plays an important role in the progression of colorectal cancer.

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