Hepatitis B virus X protein related lncRNA WEE2-AS1 promotes hepatocellular carcinoma proliferation and invasion

Zhigang Hu; Pinbo Huang; Yongcong Yan; Zhenyu Zhou; Jie Wang; Gang Wu

doi:10.1016/j.bbrc.2018.11.091

Hepatitis B virus X protein related lncRNA WEE2-AS1 promotes hepatocellular carcinoma proliferation and invasion

Biochem Biophys Res Commun. 2019 Jan 1;508(1):79-86. doi: 10.1016/j.bbrc.2018.11.091. Epub 2018 Nov 22.

Authors

Zhigang Hu¹, Pinbo Huang², Yongcong Yan³, Zhenyu Zhou³, Jie Wang², Gang Wu⁴

Affiliations

¹ Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
² Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
³ Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
⁴ Department of Hepatobiliary Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. Electronic address: [email protected].

PMID: 30471857
DOI: 10.1016/j.bbrc.2018.11.091

Abstract

Hepatitis B virus X protein (HBx) is involved in the initiation and progression of hepatocellular carcinoma (HCC) by regulating the host protein-coding genes. In this study, we showed that HBx altered the expression of lncRNAs to promote the progression of HCC. lncRNA microarray and quantitative reverse-transcription polymerase chain reactions (qRT-PCRs) were performed to identify lncRNAs that were differentially regulated by HBx in HCC cells and tissues. Protein, mRNA, and lncRNA expression analyses; cell cycle and apoptosis analyses; loss/gain-of-function analysis were performed to delineate the consequences of WEE2-AS1 upregulation in HCC cells. WEE2-AS1 over-expressed in HCC and was positively correlated to hepatitis B virus (HBV) infection, hepatic vascular invasion, poor tumor differentiation and poor patient prognosis. WEE2-AS1 also accelerated the proliferation, migration, invasion and cell cycle progression of HCC cells. Fermitin family member 3 (FERMT3) was a downstream target of WEE2-AS1. In conclusion, there is a preliminary HBx-WEE2-AS1- FERMT3 pathway which may serve as a therapeutic target for HBV-associated HCC.

Keywords: FERMT3; Hepatitis B virus x protein; Hepatocellular carcinoma; Long non-coding RNA; WEE2-AS1.

Publication types

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

MeSH terms

Adult
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology*
Cell Cycle Proteins / antagonists & inhibitors*
Cell Cycle Proteins / genetics*
Cell Cycle Proteins / metabolism
Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation
Cell Transformation, Neoplastic / genetics
Female
Gene Expression Regulation, Neoplastic
Hepatitis B virus / genetics
Hepatitis B virus / metabolism
Hepatitis B virus / pathogenicity
Hepatitis B, Chronic / complications
Humans
Liver Neoplasms / genetics*
Liver Neoplasms / metabolism
Liver Neoplasms / pathology*
Male
Membrane Proteins / genetics
Membrane Proteins / metabolism
Neoplasm Invasiveness / genetics
Neoplasm Invasiveness / pathology
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism
Protein-Tyrosine Kinases / antagonists & inhibitors*
Protein-Tyrosine Kinases / genetics*
Protein-Tyrosine Kinases / metabolism
RNA, Antisense / genetics
RNA, Antisense / metabolism
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
Signal Transduction
Trans-Activators / genetics*
Trans-Activators / metabolism*
Viral Regulatory and Accessory Proteins

Substances

Cell Cycle Proteins
FERMT3 protein, human
Membrane Proteins
Neoplasm Proteins
RNA, Antisense
RNA, Long Noncoding
Trans-Activators
Viral Regulatory and Accessory Proteins
hepatitis B virus X protein
Wee2 protein, human
Protein-Tyrosine Kinases