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CircEAF2 counteracts Epstein-Barr virus-positive diffuse large B-cell lymphoma progression via miR-BART19-3p/APC/β-catenin axis
- Source :
- Molecular Cancer, Vol 20, Iss 1, Pp 1-17 (2021), Molecular Cancer
- Publication Year :
- 2021
- Publisher :
- BMC, 2021.
-
Abstract
- Background Epstein-Barr virus (EBV) represents an important pathogenic factor of lymphoma and is significantly associated with poor clinical outcome of diffuse large B-cell lymphoma (DLBCL). Circular RNAs (circRNAs) play an essential role in lymphoma progression. However, the underlying mechanism of circRNA on DLBCL progression related to EBV remains largely unknown. 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.
- Subjects :
- Adult
Male
Cancer Research
Epstein-Barr Virus Infections
Herpesvirus 4, Human
Genes, APC
miR-BART19-3p
Biology
medicine.disease_cause
Models, Biological
Wnt signaling pathway
Mice
immune system diseases
Cell Line, Tumor
hemic and lymphatic diseases
microRNA
medicine
Biomarkers, Tumor
Animals
Humans
Epstein-Barr virus
beta Catenin
RC254-282
Aged
Cell growth
Research
circEAF2
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RNA, Circular
Diffuse large B-cell lymphoma
Middle Aged
β-catenin
medicine.disease
Epstein–Barr virus
Lymphoma
Gene Expression Regulation, Neoplastic
Disease Models, Animal
MicroRNAs
Oncology
Apoptosis
Catenin
Cancer research
Molecular Medicine
Female
Disease Susceptibility
Lymphoma, Large B-Cell, Diffuse
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 14764598
- Volume :
- 20
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular Cancer
- Accession number :
- edsair.doi.dedup.....c6235f6b8ed2ef1e753eb782e51e6914