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Recurrent Superenhancer of the Oncogene POU5F1B in Colorectal Cancers.

Authors :
Tao HC
Wang C
Ma N
Zhu X
Zhou XJ
Source :
BioMed research international [Biomed Res Int] 2021 Dec 11; Vol. 2021, pp. 5405060. Date of Electronic Publication: 2021 Dec 11 (Print Publication: 2021).
Publication Year :
2021

Abstract

Superenhancer usages in single cancer form such as colorectal cancer (CRC) may provide novel efficient targeting candidates. It is unclear whether CRC contains recurrent superenhancers that confer a predisposition to malignancy. We investigated the superenhancer profile of CRC cell line HCT116 and compared it to that of a healthy sigmoid colon. We found that HCT116 had lost most of the normal colon superenhancer activities but gained a new set of tumor-favoring superenhancers that facilitate tumor proliferation, growth signalling, and hypoxia resistance. Inhibiting the superenhancers by JQ-1 treatment had significantly decreased the colony formation capability of HCT116. Then, by comparing the superenhancer genes and robust CRC upregulated genes, we identified a superenhancer associated with a common CRC upregulated oncogene, POU5f1B . POU5f1B overexpression is related to the worse outcome in CRCs. Via performing ChIP-PCR in 35 clinical samples and investigating CRC anti-H3K27ac ChiP-seq public dataset consisting of 36 samples, we further identified that the superenhancer of oncogene POU5F1B is recurrently activated in CRCs, taking 62 and 72 per cent, respectively. Moreover, JQ-1 treatment successfully inhibited the POU5F1B expression in 5 out of 6 POU5F1B superenhancer-positive samples. Therefore, we concluded that the superenhancer activation of POU5F1B contributes partially to its high expression in CRCs, in addition to the well-known gene amplification aetiology.<br />Competing Interests: The authors declare that they have no conflicts of interest.<br /> (Copyright © 2021 Han-chuan Tao et al.)

Details

Language :
English
ISSN :
2314-6141
Volume :
2021
Database :
MEDLINE
Journal :
BioMed research international
Publication Type :
Academic Journal
Accession number :
34934770
Full Text :
https://doi.org/10.1155/2021/5405060