Recurrent Superenhancer of the Oncogene POU5F1B in Colorectal Cancers. (11th December 2021)

• Record Type: Journal Article
• Authors: Tao, Han-chuan; Wang, Cheng; Ma, Ning; Zhu, Xun; Zhou, Xiao-jun
• Other Names: Ergün Sercan Academic Editor.
• Is Part Of: BioMed research international. Volume 2021(2021)
• Publication Date: 2021-12-11
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2021/5405060
• Languages: English
• ISSNs: 2314-6133

Abstract

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.