Recurrent Superenhancer of the Oncogene POU5F1B in Colorectal Cancers

BioMed research international

Ning Ma¹  Xun Zhu²  Han-chuan Tao³  Xiao-jun Zhou⁴  Cheng Wang⁵ 

[1] Department of General Surgery, Daqing Oilfield General Hospital, Daqing, 163001 Heilongjiang, China, first-hospital.com;Department of General Surgery, Dongtai Municipal People’s Hospital of Nantong University, Yancheng, 224200 Jiangsu, China;Department of General Surgery, Dongtai Municipal People’s Hospital of Nantong University, Yancheng, 224200 Jiangsu, China;Department of General Surgery, First Affiliated Hospital of Soochow University, Soochow, Jiangsu, 215006 Jiangsu, China, suda.edu.cn;Department of General Surgery, First Affiliated Hospital of Soochow University, Soochow, Jiangsu, 215006 Jiangsu, China, suda.edu.cn;Department of Neurology, Dongtai Municipal People’s Hospital of Nantong University, Yancheng, 224200 Jiangsu, China, nsw.gov.au;

DOI  :  10.1155/2021/5405060

来源: Hindawi Publishing Corporation

【 摘 要 】

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.

【 授权许可】

CC BY