HIV gp120/Tat protein-induced epithelial-mesenchymal transition promotes the progression of cervical lesions.
Cervical cancer
Epithelial–mesenchymal transition (EMT)
HIV infection
Tat protein
gp120 protein
Journal
AIDS research and therapy
ISSN: 1742-6405
Titre abrégé: AIDS Res Ther
Pays: England
ID NLM: 101237921
Informations de publication
Date de publication:
19 11 2023
19 11 2023
Historique:
received:
10
09
2023
accepted:
25
10
2023
medline:
27
11
2023
pubmed:
20
11
2023
entrez:
20
11
2023
Statut:
epublish
Résumé
Human immunodeficiency virus (HIV) infection is associated with an elevated incidence of cervical cancer, and accelerated disease progression, but the underlying mechanisms are not well understood. This study aimed to investigate the relationship between HIV infection and epithelial-mesenchymal transition (EMT) in cervical cancer. Tissue samples from HIV-positive and negative patients with cervical intraepithelial neoplasia (CIN) and cervical cancer were analyzed for EMT-related proteins. Human cervical cancer SiHa cells were treated with HIV Tat and gp120 proteins to test their effects on EMT, migration, and invasion. HIV-positive patients had lower E-cadherin and cytokeratin, and higher N-cadherin and vimentin levels than HIV-negative patients. HIV Tat and gp120 proteins induced EMT, migration, and invasion in SiHa cells. Transcriptome sequencing analysis revealed that, compared to the control group, the protein-treated group showed upregulation of 22 genes and downregulation of 77 genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed the involvement of the Wnt signaling pathway in EMT. Further analysis of gene expression related to this pathway revealed upregulation of DVL1, TCF7, KRT17, and VMAC, while GSK3β, SFRP2, and CDH1 were downregulated. Immunofluorescence assay demonstrated that HIVgp120 and Tat proteins treatment induced elevated β-catenin expression with nuclear accumulation in SiHa cells. The treatment of SiHa cells with HIV Tat and gp120 proteins induces EMT and activates the Wnt/β-catenin pathway, suggesting that the Wnt/β-catenin pathway may play a crucial role in promoting EMT progression in cervical lesion tissues of HIV-infected patients.
Sections du résumé
BACKGROUND
Human immunodeficiency virus (HIV) infection is associated with an elevated incidence of cervical cancer, and accelerated disease progression, but the underlying mechanisms are not well understood. This study aimed to investigate the relationship between HIV infection and epithelial-mesenchymal transition (EMT) in cervical cancer.
METHODS
Tissue samples from HIV-positive and negative patients with cervical intraepithelial neoplasia (CIN) and cervical cancer were analyzed for EMT-related proteins. Human cervical cancer SiHa cells were treated with HIV Tat and gp120 proteins to test their effects on EMT, migration, and invasion.
RESULTS
HIV-positive patients had lower E-cadherin and cytokeratin, and higher N-cadherin and vimentin levels than HIV-negative patients. HIV Tat and gp120 proteins induced EMT, migration, and invasion in SiHa cells. Transcriptome sequencing analysis revealed that, compared to the control group, the protein-treated group showed upregulation of 22 genes and downregulation of 77 genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed the involvement of the Wnt signaling pathway in EMT. Further analysis of gene expression related to this pathway revealed upregulation of DVL1, TCF7, KRT17, and VMAC, while GSK3β, SFRP2, and CDH1 were downregulated. Immunofluorescence assay demonstrated that HIVgp120 and Tat proteins treatment induced elevated β-catenin expression with nuclear accumulation in SiHa cells.
CONCLUSIONS
The treatment of SiHa cells with HIV Tat and gp120 proteins induces EMT and activates the Wnt/β-catenin pathway, suggesting that the Wnt/β-catenin pathway may play a crucial role in promoting EMT progression in cervical lesion tissues of HIV-infected patients.
Identifiants
pubmed: 37981694
doi: 10.1186/s12981-023-00577-1
pii: 10.1186/s12981-023-00577-1
pmc: PMC10657494
doi:
Substances chimiques
beta Catenin
0
Gene Products, tat
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
82Subventions
Organisme : the Science and Technology Program of Guangzhou
ID : 202201020255
Organisme : the Science and Technology Program of Guangzhou
ID : SL2023a03J0788
Organisme : the Health Science and Technology Project of Guangzhou
ID : 20211A011041
Informations de copyright
© 2023. The Author(s).
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