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CXCR4 induces cell autophagy and maintains EBV latent infection in EBVaGC
- Source :
- Theranostics
- Publication Year :
- 2020
- Publisher :
- Ivyspring International Publisher, 2020.
-
Abstract
- Rationale: Epstein-Barr virus (EBV) is found in ~7% of gastric carcinoma cases worldwide, and all tumour cells harbour the clonal EBV genome. EBV can regulate pathways and protein expression to induce gastric carcinoma; however, the molecular mechanism underlying EBV-associated gastric carcinoma (EBVaGC) remains elusive. Methods: GEO microarray and molecular experiments were performed to compare CXCR4 expression between EBV-positive and EBV-negative gastric carcinoma (EBVnGC). Transfections with LMP2A plasmid or siRNA were carried out to assess the role of LMP2A in CXCR4 expression. The effects and mechanisms of CXCR4 on cell autophagy were analysed in vitro using molecular biological and cellular approaches. Additionally, we also determined the regulatory role of CXCR4 in latent EBV infection. Results: CXCR4 expression was significantly upregulated in EBVaGC tissues and cell lines. LMP2A could induce AKT phosphorylation to increase NRF1 expression, thereby binding to the CXCR4 promoter to increase its transcriptional level. Moreover, CXCR4 promoted ZEB1 expression to upregulate ATG7 synthesis, which could then activate autophagy. Moreover, CXCR4 increased the number of cells entering the G2/M phase and inhibited cell apoptosis via the autophagy pathway. Finally, CXCR4 knockdown was associated with elevated BZLF1 expression, but this effect was not influenced by autophagy. Conclusions: Our data suggested new roles for CXCR4 in autophagy and EBV replication in EBVaGC, which further promoted cell survival and persistent latent infection. These new findings can lead to further CXCR4-based anticancer therapy.
- Subjects :
- 0301 basic medicine
Male
Epstein-Barr Virus Infections
Herpesvirus 4, Human
Carcinogenesis
Cell
Medicine (miscellaneous)
Datasets as Topic
CXCR4
0302 clinical medicine
hemic and lymphatic diseases
Promoter Regions, Genetic
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Oligonucleotide Array Sequence Analysis
Gene knockdown
Middle Aged
EBVaGC
Immunohistochemistry
Up-Regulation
Gene Expression Regulation, Neoplastic
medicine.anatomical_structure
030220 oncology & carcinogenesis
Gene Knockdown Techniques
RNA, Viral
Female
Research Paper
Receptors, CXCR4
Biology
BZLF1
Viral Matrix Proteins
03 medical and health sciences
Downregulation and upregulation
EBV
Stomach Neoplasms
Cell Line, Tumor
medicine
Autophagy
Humans
Host Microbial Interactions
Gene Expression Profiling
Carcinoma
030104 developmental biology
Apoptosis
Cell culture
Gastric Mucosa
Cancer research
Latent Infection
Subjects
Details
- Language :
- English
- ISSN :
- 18387640
- Volume :
- 10
- Issue :
- 25
- Database :
- OpenAIRE
- Journal :
- Theranostics
- Accession number :
- edsair.doi.dedup.....b86bd6acbbf0e4106ad2b1ddf3c96c22