Epigenetics of oral and oropharyngeal cancers (Review)

Russo, Daniela; Merolla, Francesco; Varricchio, Silvia; Salzano, Giovanni; Zarrilli, Giovanni; Mascolo, Massimo; Strazzullo, Viviana; Crescenzo, Rosa Maria Di; Celetti, Angela; Ilardi, Gennaro

doi:10.3892/br.2018.1136

Cited by 24 publications

(19 citation statements)

References 110 publications

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“…In this context, the role of non-coding RNAs, of which miRNAs are the most studied, has been recently acquiring remarkable importance in the development of several pathologies, including cancer [26,27,28]. In particular, several studies demonstrated that miRNAs, a class of small non-coding RNAs with a length of 20–22 nucleotides, are involved in cancer, including that of oral cavity cancer, inducing epigenetic modifications altering key cellular processes, such as cell differentiation, growth, apoptosis and drug resistance [29,30]. Notably, miRNAs are able to regulate gene expression by controlling mRNA translation, either by translational repression of the targeted mRNA or by enhancing its degradation through an RNA interference mechanism [31].…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel MicroRNAs and Their Diagnostic and Prognostic Significance in Oral Cancer

Falzone

Lupo

Rosa

et al. 2019

Cancers

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Background: Oral cancer is one of the most prevalent cancers worldwide. Despite that the oral cavity is easily accessible for clinical examinations, oral cancers are often not promptly diagnosed. Furthermore, to date no effective biomarkers are available for oral cancer. Therefore, there is an urgent need to identify novel biomarkers able to improve both diagnostic and prognostic strategies. In this context, the development of innovative high-throughput technologies for molecular and epigenetics analyses has generated a huge amount of data that may be used for the identification of new cancer biomarkers. Methods: In the present study, GEO DataSets and TCGA miRNA profiling datasets were analyzed in order to identify miRNAs with diagnostic and prognostic significance. Furthermore, several computational approaches were adopted to establish the functional roles of these miRNAs. Results: The analysis of datasets allowed for the identification of 11 miRNAs with a potential diagnostic role for oral cancer. Additionally, eight miRNAs associated with patients’ prognosis were also identified; six miRNAs predictive of patients’ overall survival (OS) and one, hsa-miR-let.7i-3p, associated with tumor recurrence. Conclusion: The integrated analysis of different miRNA expression datasets allows for the identification of a set of miRNAs that, after validation, may be used for the early detection of oral cancers.

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Section: Introductionmentioning

confidence: 99%

Identification of Novel MicroRNAs and Their Diagnostic and Prognostic Significance in Oral Cancer

Falzone

Lupo

Rosa

et al. 2019

Cancers

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show abstract

“…As the incidence of HPV-associated oropharyngeal carcinoma continues to rise, expanding our knowledge of epigenetic drivers that regulate HPV pathogenesis in the oropharyngeal epithelium is an important area of future research. Even though epigenetic modifications in HPV-associated oropharyngeal cancers, including DNA methylation and histone modifications, have been reported [152], the role of the DNA damage response in the epigenetic regulation of the viral life cycle in oropharyngeal epithelium remains uncharacterized. This is especially important, as recent studies indicate that the viral genome is episomal in a large number of head and neck cancers [153].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Regulation of the Human Papillomavirus Life Cycle

Mac

Moody

2020

Pathogens

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Persistent infection with certain types of human papillomaviruses (HPVs), termed high risk, presents a public health burden due to their association with multiple human cancers, including cervical cancer and an increasing number of head and neck cancers. Despite the development of prophylactic vaccines, the incidence of HPV-associated cancers remains high. In addition, no vaccine has yet been licensed for therapeutic use against pre-existing HPV infections and HPV-associated diseases. Although persistent HPV infection is the major risk factor for cancer development, additional genetic and epigenetic alterations are required for progression to the malignant phenotype. Unlike genetic mutations, the reversibility of epigenetic modifications makes epigenetic regulators ideal therapeutic targets for cancer therapy. This review article will highlight the recent advances in the understanding of epigenetic modifications associated with HPV infections, with a particular focus on the role of these epigenetic changes during different stages of the HPV life cycle that are closely associated with activation of DNA damage response pathways.

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“…Oral/oropharyngeal carcinogenesis mostly depends on environmental factors, such as tobacco and alcohol abuse, particularly in the oral cavity, and persistent infection from HR-HPV in a rising percentage of oropharyngeal cancers. Thus far, only a few reliable prognostic markers have been reported, alone or in combination, for OSCC and OPSCC [35,36,37,38,39].…”

Section: Discussionmentioning

confidence: 99%

CAF-1 Subunits Levels Suggest Combined Treatments with PARP-Inhibitors and Ionizing Radiation in Advanced HNSCC

Morra

Merolla

Picardi

et al. 2019

Cancers

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Oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas show high morbidity and mortality rates. We aimed to investigate the role of the “Chromatin Assembly Factor-1” (CAF-1) p60 and p150 subunits, involved in DNA repair and replication, in OSCC and OPSCC progression and in response to Poly(ADP-ribose) polymerase (PARP)-inhibitors and exposure to ionizing radiation (IR). We immunostained tissue microarrays (TMAs), including 112 OSCC and 42 OPSCC, with anti-CAF-1/p60 and anti-CAF-1/p150 specific antibodies, correlating their expression with prognosis. Moreover, we assessed the sensitivity to PARP inhibitors and the double-strand breaks repair proficiency by cell viability and HR reporter assays, respectively, in HPV-positive and HPV-negative cell lines upon CAF-1/p60 and CAF-1/p150 depletion. The immunohistochemical analysis revealed a significant prognostic value of both tissue biomarkers combined expression in OSCC but not in OPSCC. In in vitro studies, the p60/150 CAF-1 subunits’ depletion impaired the proficiency of Homologous Recombination DNA damage repair, inducing sensitivity to the PARP-inhibitors, able to sensitize both the cell lines to IR. These results indicate that regardless of the prognostic meaning of p60/p150 tissue expression, the pharmacological depletion of CAF-1 complex’s function, combined to PARP-inhibitors and/or IR treatment, could represent a valid therapeutic strategy for squamous cell carcinomas of head and neck region.

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Epigenetics of oral and oropharyngeal cancers (Review)

Cited by 24 publications

References 110 publications

Identification of Novel MicroRNAs and Their Diagnostic and Prognostic Significance in Oral Cancer

Identification of Novel MicroRNAs and Their Diagnostic and Prognostic Significance in Oral Cancer

Epigenetic Regulation of the Human Papillomavirus Life Cycle

CAF-1 Subunits Levels Suggest Combined Treatments with PARP-Inhibitors and Ionizing Radiation in Advanced HNSCC

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