LncRNA FOXD2-AS1 plays an oncogenic role in hepatocellular carcinoma through epigenetically silencing CDKN1B(p27) via EZH2

Kangdi Xu; Zhihao Zhang; Junjie Qian; Shuai Wang; Shengyong Yin; Haiyang Xie; Lin Zhou; Shusen Zheng

doi:10.1016/j.yexcr.2019.04.016

LncRNA FOXD2-AS1 plays an oncogenic role in hepatocellular carcinoma through epigenetically silencing CDKN1B(p27) via EZH2

Exp Cell Res. 2019 Jul 15;380(2):198-204. doi: 10.1016/j.yexcr.2019.04.016. Epub 2019 Apr 17.

Authors

Kangdi Xu¹, Zhihao Zhang¹, Junjie Qian¹, Shuai Wang¹, Shengyong Yin², Haiyang Xie², Lin Zhou³, Shusen Zheng⁴

Affiliations

¹ Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery First Affiliated Hospital, School of Medicine, Zhejiang University, PR China; NHFPC Key Laboratory of Combined Multi-organ Transplantation, PR China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Chinese Academy of Medical Sciences, PR China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, PR China.
² NHFPC Key Laboratory of Combined Multi-organ Transplantation, PR China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Chinese Academy of Medical Sciences, PR China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, PR China.
³ Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Chinese Academy of Medical Sciences, PR China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, PR China; Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Hangzhou, Zhejiang, 310003, PR China. Electronic address: zhoulin99@zju.edu.cn.
⁴ Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery First Affiliated Hospital, School of Medicine, Zhejiang University, PR China; NHFPC Key Laboratory of Combined Multi-organ Transplantation, PR China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Chinese Academy of Medical Sciences, PR China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, PR China; Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Hangzhou, Zhejiang, 310003, PR China. Electronic address: shusenzheng@zju.edu.cn.

PMID: 31004581
DOI: 10.1016/j.yexcr.2019.04.016

Abstract

Accumulating reports suggest that long noncoding RNAs (lncRNAs) play critical roles in the progression of many tumors. In this study, we explored the expression level of lncRNA FOXD2-AS1 in the tumorigenesis of hepatocellular carcinoma (HCC). The data indicated that FOXD2-AS1 expression was increased in HCC specimens and cell lines. Furthermore, aberrant expression was correlated with tumor number and tumor size in HCC patients. Silencing FOXD2-AS1 arrest cell cycle in the G0/G1 phase, inhibited colony formation, cell proliferation and suppressed the in vivo growth of subcutaneous tumors. Our results revealed that FOXD2-AS1 could epigenetically silence CDKN1B by recruiting EZH2 to CDKN1B promoter region. Knocking down CDKN1B could restore the carcinogenic effect of FOXD2-AS1 on HCC. Collectively, our data suggested that FOXD2-AS1 could be new target for therapies or prognostic biomarker in hepatocellular carcinoma.

Keywords: CDKN1B; Cell proliferation; EZH2; FOXD2-AS1; Hepatocellular carcinoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Cell Proliferation
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p27 / genetics*
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Enhancer of Zeste Homolog 2 Protein / genetics*
Enhancer of Zeste Homolog 2 Protein / metabolism
Epigenesis, Genetic / genetics*
Female
Gene Silencing
Humans
Liver Neoplasms / genetics*
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Liver Neoplasms, Experimental / genetics
Liver Neoplasms, Experimental / metabolism
Liver Neoplasms, Experimental / pathology
Male
Mice
Middle Aged
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism

Substances

CDKN1B protein, human
RNA, Long Noncoding
long non-coding RNA FOXD2-AS1, human
Cyclin-Dependent Kinase Inhibitor p27
EZH2 protein, human
Enhancer of Zeste Homolog 2 Protein