Comparative Gene Expression Profiling of Tobacco-Associated HPV-Positive versus Negative Oral Squamous Carcinoma Cell Lines.
Int J Med Sci
; 17(1): 112-124, 2020.
Article
em En
| MEDLINE
| ID: mdl-31929745
ABSTRACT
Background:
HPV-positive oral squamous cell carcinomas (OSCCs) are specific biological and clinical entities, characterized by a more favorable prognosis compared to HPV-negative OSCCs and occurring generally in non-smoking and non-drinking younger individuals. However, poor information is available on the molecular and the clinical behavior of HPV-positive oral cancers occurring in smoking/drinking subjects. Thus, this study was designed to compare, at molecular level, two OSCC cell lines, both derived from drinking and smoking individuals and differing for presence/absence of HPV infection.Methods:
HPV-negative UPCI-SCC-131 and HPV16-positive UPCI-SCC-154 cell lines were compared by whole genome gene expression profiling and subsequently studied for activation of Wnt/ßCatenin signaling pathway by the expression of several Wnt-target genes, ßCatenin intracellular localization, stem cell features and miRNA let-7e. Gene expression data were validated in head and neck squamous cell carcinoma (HNSCC) public datasets.Results:
Gene expression analysis identified Wnt/ßCatenin pathway as the unique signaling pathway more active in HPV-negative compared to HPV-positive OSCC cells and this observation was confirmed upon evaluation of several Wnt-target genes (i.e., Cyclin D1, Cdh1, Cdkn2a, Cd44, Axin2, c-Myc and Tcf1). Interestingly, HPV-negative OSCC cells showed higher levels of total ßCatenin and its active form, increase of its nuclear accumulation and more prominent stem cell traits. Furthermore, miRNA let-7e was identified as potential upstream regulator responsible for the downregulation of Wnt/ßCatenin signaling cascade since its silencing in UPCI-SCC-154 cell resulted in upregulation of Wnt-target genes. Finally, the analysis of two independent gene expression public datasets of human HNSCC cell lines and tumors confirmed that Wnt/ßCatenin pathway is more active in HPV-negative compared to HPV-positive tumors derived from individuals with smoking habit.Conclusions:
These data suggest that lack of HPV infection is associated with more prominent activation of Wnt/ßCatenin signaling pathway and gain of stem-like traits in tobacco-related OSCCs.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Nicotiana
/
Infecções por Papillomavirus
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Papillomavirus Humano 16
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Carcinoma de Células Escamosas de Cabeça e Pescoço
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Int J Med Sci
Assunto da revista:
MEDICINA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Itália