YY1 promotes colorectal cancer proliferation through the miR-526b-3p/E2F1 axis

Zejun Fang; Hua Yang; Dan Chen; Xiaoying Shi; Qinqiu Wang; Chaoju Gong; Xi Xu; Hong Liu; Min Lin; Junxiao Lin; Chengfu Xu; Jimin Shao

YY1 promotes colorectal cancer proliferation through the miR-526b-3p/E2F1 axis

Am J Cancer Res. 2019 Dec 1;9(12):2679-2692. eCollection 2019.

Authors

Zejun Fang^{1

2

3}, Hua Yang¹, Dan Chen¹, Xiaoying Shi¹, Qinqiu Wang¹, Chaoju Gong⁴, Xi Xu⁵, Hong Liu^{6

7}, Min Lin^{2

3}, Junxiao Lin^{2

3}, Chengfu Xu¹, Jimin Shao⁸

Affiliations

¹ Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
² Central Laboratory, Sanmenwan Branch, The First Affiliated Hospital, College of Medicine, Zhejiang University Sanmen, China.
³ Central Laboratory, Sanmen People's Hospital of Zhejiang Province Sanmen, China.
⁴ Central Laboratory, The Municipal Affiliated Hospital of Xuzhou Medical University Xuzhou, China.
⁵ Department of Pathology, The Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
⁶ Zhejiang Normal University, Jinhua People's Hospital Joint Center for Biomedical Research Jinhua, China.
⁷ The Affiliated Hospital of Jinhua Polytechnic College Jinhua, China.
⁸ Department of Pathology and Pathophysiology, College of Medicine, Zhejiang University Hangzhou, China.

PMID: 31911854
PMCID: PMC6943347

Abstract

We previously reported that E2F1 expression is up-regulated and positively correlated with the malignant phenotypes of colorectal cancer (CRC). However, the underlying mechanisms leading to the aberrant up-regulation of E2F1 in CRC have not been clarified. In this study, we observed that miR-526b-3p directly targets the 3'UTR of E2f1 mRNA, leading to reduced E2F1 expression. Overexpression of miR-526b-3p inhibited the proliferation of CRC cells by decreasing the level of E2F1. We also found that the Ying Yang 1 (YY1)-dependent transcriptional suppression of miR-526b-3p is responsible for the up-regulation of E2F1 in CRC, in which YY1 binds to the promoter of miR-526b gene and recruits histone deacetylase (HDAC). Knockdown of YY1 led to cell cycle arrest and diminished colony formation in CRC cells partly through relieving the miR-526b-3p suppression. Clinical analysis showed that YY1 and E2F1 were negatively correlated with miR-526b-3p in CRC tissues. Moreover, a high level of YY1 and E2F1, or a low level of miR-526b-3p, predicted poor survival of CRC patients. In conclusion, our findings highlight the dysregulation of the YY1/miR-526b-3p/E2F1 axis in CRC development, implicating a novel regulatory pathway for E2F1 as a potential therapeutic target in CRC.

Keywords: E2F1; Ying Yang 1; colorectal cancer; miR-526b-3p; proliferation.