Abstract | BACKGROUND: METHODS:
CircRNA was screened by high-throughput sequencing in tumor samples of 12 patients with DLBCL according to EBV infection status. Expression of circEAF2, as well as the relationship with clinical characteristics and prognosis, were further analyzed in tumor samples of 100 DLBCL patients using quantitative real-time PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of circEAF2 both in vitro and in vivo. The underlying mechanism of circRNA on DLBCL progression were further determined by RNA sequencing, RNA pull down assay, dual- luciferase reporter assay, rescue experiments and western blotting. RESULTS: We identified a novel circRNA circEAF2, which was downregulated in EBV + DLBCL and negatively correlated with EBV infection and DLBCL progression. In EBV-positive B lymphoma cells, circEAF2 overexpression induced lymphoma cell apoptosis and sensitized lymphoma cells to epirubicin. As mechanism of action, circEAF2 specifically targeted EBV-encoded miR-BART19-3p, upregulated APC, and suppressed downstream β- catenin expression, resulting in inactivation of Wnt signaling pathway and inhibition of EBV + DLBCL cell proliferation. In EBV-positive B- lymphoma murine models, xenografted tumors with circEAF2 overexpression presented decreased Ki-67 positivity, increased cell apoptosis and retarded tumor growth. CONCLUSIONS: CircEAF2 counteracted EBV + DLBCL progression via miR-BART19-3p/APC/β- catenin axis, referring circEAF2 as a potential prognostic biomarker. Therapeutic targeting EBV-encoded miRNA may be a promising strategy in treating EBV-associated lymphoid malignancies.
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Authors | Chen-Xing Zhao, Zi-Xun Yan, Jing-Jing Wen, Di Fu, Peng-Peng Xu, Li Wang, Shu Cheng, Jian-da Hu, Wei-Li Zhao |
Journal | Molecular cancer
(Mol Cancer)
Vol. 20
Issue 1
Pg. 153
(12 01 2021)
ISSN: 1476-4598 [Electronic] England |
PMID | 34852843
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2021. The Author(s). |
Chemical References |
- Biomarkers, Tumor
- EAF2 protein, human
- MIRN19 microRNA, human
- MicroRNAs
- RNA, Circular
- Transcription Factors
- beta Catenin
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Topics |
- Adult
- Aged
- Animals
- Biomarkers, Tumor
- Cell Line, Tumor
- Disease Models, Animal
- Disease Susceptibility
- Epstein-Barr Virus Infections
(complications)
- Female
- Gene Expression Regulation, Neoplastic
- Genes, APC
- Herpesvirus 4, Human
- Humans
- Lymphoma, Large B-Cell, Diffuse
(etiology, metabolism, pathology, therapy)
- Male
- Mice
- MicroRNAs
(genetics)
- Middle Aged
- Models, Biological
- RNA, Circular
(genetics)
- Transcription Factors
(genetics)
- Wnt Signaling Pathway
- beta Catenin
(metabolism)
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