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HPV16 E6 oncoprotein-induced upregulation of lncRNA GABPB1-AS1 facilitates cervical cancer progression by regulating miR-519e-5p/Notch2 axis

Authors :
Xiangyun Li
Jiangmin Lv
Yi Ren
Jianrong Li
Rongying Ou
Xuan Liu
Mingfen Lv
Wenfeng Li
Ye Zhao
Jinduo Zhao
Liang Zhao
Yunsheng Xu
Source :
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 34(10)
Publication Year :
2020

Abstract

Human papillomaviruses 16 (HPV16) is the primary causative agent of cervical cancer (CC). E6 oncoprotein plays a crucial role in cervical carcinogenesis and commonly cause the dysregulation of the long noncoding RNAs (lncRNAs) expression. However, the biological function of lncRNAs in HPV16-related CC remains largely unexplored. In the present study HPV16 E6-induced differential expression of lncRNAs, miRNA, and mRNA were identified using microarray-based analysis and verified in tumor r cell lines and tumor tissues, and the function of lncRNA in CC was investigated in vitro and in vivo. We found that an lncRNA, named GABPB1-AS1, was significantly upregulated in HPV16-positive CC tissues and cell lines. GABPB1-AS1 expression in HPV16-positive CC tissues was positively associated with tumor size, lymph node metastasis, and FIGO stage. High expression of GABPB1-AS1 was correlated with a poor prognosis for HPV16-positive CC patients. Functionally, E6-induced GABPB1-AS1 overexpression facilitated CC cells proliferation and invasion in vitro and in vivo. Mechanistically, GABPB1-AS1 acted as a competing endogenous RNA (ceRNA) by sponging miR-519e-5p, resulting in the de-repression of its target gene Notch2 which is well known as an oncogene. Therefore, GABPB1-AS1 functioned as a tumor activator in CC pathogenesis by binding to miR-519e-5p and destroying its tumor suppressive function. Collectively, current results demonstrate that GABPB1-AS1 is associated with CC progression, and may be a promising biomarker or target for the clinical management of CC.

Details

ISSN :
15306860
Volume :
34
Issue :
10
Database :
OpenAIRE
Journal :
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES
Accession number :
edsair.doi.dedup.....6829633acff8ea5c63fe49e649f81de7