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Insights into Oral Squamous Cell Carcinoma
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Insights into Oral Squamous Cell Carcinoma

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 December 2024 | Viewed by 8298

Special Issue Editor

Dr. Emil Dediol

E-Mail Website
Guest Editor
Department of Maxillofacial Surgery, Clinical Hospital Dubrava, 10000 Zagreb, Croatia
Interests: head and neck cancer; oral cancer; head & neck pathology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Oral cancer affects various anatomical sites inside the oral cavity, with tongue being the most prevalent site in most countries and geographical regions in the world. Other affected sites can differ depending on whether the etiology is alcohol and smoking (floor of the mouth and gingiva), or tobacco and betel nut chewing (buccal mucosa and palate). The mainstay of oral cancer treatment is still primarily surgery, and this has not changed in the last 70 years.

We still poorly understand molecular changes that occurs during the development and progression of oral cancer and the relevant molecular markers have been very heterogenous. This is why targeted oncological therapy has yet to be successful in oral cancer like for other types of cancer. Research regarding molecular mechanisms that promote oral carcinogenesis should be further investigated.

The purpose of this Special Issue is to give more insights into the molecular mechanisms of oral cancer regarding epigenetics, prognostic molecular markers and possible molecular markers regarding oncological therapy. Original research articles and reviews are welcome.

Dr. Emil Dediol
Guest Editor

Manuscript Submission Information

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Keywords

  • oral cancer
  • tongue cancer
  • prognostic markers
  • epigenetics
  • molecular changes
  • neck metastasis
  • survival
  • miRNA
  • buccal cancer
  • screening

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Published Papers (4 papers)

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Research

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16 pages, 7600 KiB  
Article
Betaine Induces Apoptosis and Inhibits Invasion in OSCC Cell Lines
by Promphakkon Kulthanaamondhita, Chatvadee Kornsuthisopon, Ajjima Chansaenroj, Ekarat Phattarataratip, Kraisorn Sappayatosok, Lakshman Samaranayake and Thanaphum Osathanon
Int. J. Mol. Sci. 2024, 25(19), 10295; https://doi.org/10.3390/ijms251910295 - 25 Sep 2024
Viewed by 947
Abstract
Betaine, known as trimethylglycine, is a non-toxic natural substance reported to affect cancer cell responses. This study delves into the impact of betaine on the survival, proliferation, and invasion of oral squamous cell carcinoma (OSCC) cells in vitro. Human OSCC cells (HSC-4 and [...] Read more.
Betaine, known as trimethylglycine, is a non-toxic natural substance reported to affect cancer cell responses. This study delves into the impact of betaine on the survival, proliferation, and invasion of oral squamous cell carcinoma (OSCC) cells in vitro. Human OSCC cells (HSC-4 and HSC-7) were subjected to varying concentrations of betaine, and their viability and proliferation were assessed through colourimetric MTT and colony-forming unit assays. Cell cycle progression and cell apoptosis were also investigated using flow cytometry, while cell migration and invasion were examined using a transwell migration assay, and the mRNA expression was evaluated by a quantitative polymerase chain reaction. Finally, proteomic analysis was conducted through liquid chromatography-tandem mass spectrometry on the extracted protein component of the cells. Results indicate that betaine effectively suppressed OSCC proliferation and colony formation. It triggered early apoptosis without disrupting cell cycle progression, reduced cell migration, and inhibited invasion. Betaine exposure led to significantly decreased mRNA levels of MMP1, MMP2, and MMP9 while downregulating FN1, a gene linked to epithelial-to-mesenchymal transition. Proteomic analysis revealed 9240 differentially expressed up/downregulated proteins in cells treated with betaine. The significantly upregulated proteins were associated with ATP-binding cassette (ABC) transporters, while the down-regulated proteins were associated with G protein-coupled receptors (GPCR) ligand binding. In conclusion, betaine exhibits potent anti-cancer properties by attenuating OSCC cell proliferation and mitigating invasion. Exploring this natural product as an adjunct for managing oral squamous cell carcinoma shows promise, although further investigations are needed to fully elucidate its functionality. Full article
(This article belongs to the Special Issue Insights into Oral Squamous Cell Carcinoma)
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23 pages, 6319 KiB  
Article
PAICS/DYRK3 Multienzyme Interactions as Coregulators of Purinosome Formation and Metabolism on Radioresistance in Oral Squamous Cell Carcinoma
by Chin-Sheng Huang, Ming-Shou Hsieh, Vijesh Kumar Yadav, Yang-Che Wu, Shao-Cheng Liu, Chi-Tai Yeh and Mao-Suan Huang
Int. J. Mol. Sci. 2023, 24(24), 17346; https://doi.org/10.3390/ijms242417346 - 11 Dec 2023
Cited by 1 | Viewed by 1481
Abstract
Oral squamous cell carcinoma (OSCC) is a prevalent type of oral cancer. While therapeutic innovations have made strides, radioresistance persists as a significant hindrance in OSCC treatment. Despite identifying numerous targets that could potentially suppress the oncogenic attributes of OSCC, the exploration of [...] Read more.
Oral squamous cell carcinoma (OSCC) is a prevalent type of oral cancer. While therapeutic innovations have made strides, radioresistance persists as a significant hindrance in OSCC treatment. Despite identifying numerous targets that could potentially suppress the oncogenic attributes of OSCC, the exploration of oncogenic protein kinases for cancer therapy remains limited. Consequently, the functions of many kinase proteins in OSCC continue to be largely undetermined. In this research, we aim to disclose protein kinases that target OSCC and elaborate their roles and molecular mechanisms. Through the examination of the kinome library of radiotherapy-resistant/sensitive OSCC cell lines (HN12 and SAS), we identified a key gene, the tyrosine phosphorylation-regulated kinase 3 (DYRK3), a member of the DYRK family. We developed an in vitro cell model, composed of radiation-resistant OSCC, to scrutinize the clinical implications and contributions of DYRK3 and phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (PAICS) signaling in OSCC. This investigation involves bioinformatics and human tissue arrays. We seek to comprehend the role of DYRK3 and PAICS signaling in the development of OSCC and its resistance to radiotherapy. Various in vitro assays are utilized to reveal the essential molecular mechanism behind radiotherapy resistance in connection with the DYRK3 and PAICS interaction. In our study, we quantified the concentrations of DYRK3 and PAICS proteins and tracked the expression levels of key pluripotency markers, particularly PPAT. Furthermore, we extended our investigation to include an analysis of Glut-1, a gene recognized for its linkage to radioresistance in oral squamous cell carcinoma (OSCC). Furthermore, we conducted an in vivo study to affirm the impact of DYRK3 and PAICS on tumor growth and radiotherapy resistance, focusing particularly on the role of DYRK3 in the radiotherapy resistance pathway. This focus leads us to identify new therapeutic agents that can combat radiotherapy resistance by inhibiting DYRK3 (GSK-626616). Our in vitro models showed that inhibiting PAICS disrupts purinosome formation and influences the survival rate of radiation-resistant OSCC cell lines. These outcomes underscore the pivotal role of the DYRK3/PAICS axis in directing OSCC radiotherapy resistance pathways and, as a result, influencing OSCC progression or therapy resistance. Our findings also reveal a significant correlation between DYRK3 expression and the PAICS enzyme in OSCC radiotherapy resistance. Full article
(This article belongs to the Special Issue Insights into Oral Squamous Cell Carcinoma)
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Review

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11 pages, 800 KiB  
Review
Impact of Human Papillomavirus on microRNA-21 Expression in Oral and Oropharyngeal Cancer—A Systematic Review
by Mario Kordic, Dinko Martinovic, Ema Puizina, Josko Bozic, Zeljko Zubcic and Emil Dediol
Int. J. Mol. Sci. 2024, 25(15), 8038; https://doi.org/10.3390/ijms25158038 - 23 Jul 2024
Viewed by 929
Abstract
Recently, microRNAs (miR) were identified to have potential links with oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) oncogenesis, specifically miR-21. Since HPV is a major risk factor for the development of these diseases, we aimed to search the literature [...] Read more.
Recently, microRNAs (miR) were identified to have potential links with oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) oncogenesis, specifically miR-21. Since HPV is a major risk factor for the development of these diseases, we aimed to search the literature regarding miR-21 expression in both HPV-positive and HPV-negative OSCC/OPSCC. The search was performed in the PubMed (MEDLINE), Scopus, Web of Science, and Cochrane electronic databases. The research question was as follows: Is there a difference in the tissue expression of miR-21 between patients with HPV-positive and those with HPV-negative OSCC/OPSCC? After conducting a meticulous search strategy, four studies were included, and they had a pooled sample size of 621 subjects with OSCC and/or OPSCC. Three studies did not find any significant difference in miR-21 expression between HPV-positive and HPV-negative OSCC/OPSCC. The findings of this systematic review showed that there are no differences in miR-21 expression between HPV-positive and HPV-negative OSCC/OPSCC. Nevertheless, it is worth noting that there are still insufficient studies regarding this important subject, because understanding how HPV influences miR-21 expression and its downstream effects can provide insights into the molecular mechanisms underlying OSCC/OPSCC development and progression. Full article
(This article belongs to the Special Issue Insights into Oral Squamous Cell Carcinoma)
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12 pages, 683 KiB  
Review
Salivary Biomarkers for Oral Cancer Detection: An Exploratory Systematic Review
by Daniel Bastías, Alejandro Maturana, Constanza Marín, René Martínez and Sven Eric Niklander
Int. J. Mol. Sci. 2024, 25(5), 2634; https://doi.org/10.3390/ijms25052634 - 23 Feb 2024
Cited by 8 | Viewed by 4367
Abstract
Different efforts have been made to find better and less invasive methods for the diagnosis and prediction of oral cancer, such as the study of saliva as a source of biomarkers. The aim of this study was to perform a scoping review about [...] Read more.
Different efforts have been made to find better and less invasive methods for the diagnosis and prediction of oral cancer, such as the study of saliva as a source of biomarkers. The aim of this study was to perform a scoping review about salivary molecules that have been assessed as possible biomarkers for the diagnosis of oral squamous cell carcinoma (OSCC). A search was conducted using EBSCO, PubMed (MEDLINE), Scopus, and Web of Science. The research question was as follows: which molecules present in saliva have utility to be used as biomarkers for the early detection of oral cancer? Sixty-two studies were included. Over 100 molecules were assessed. Most of the markers were oriented towards the early diagnosis of OSCC and were classified based on their ability for detecting OSCC and oral potentially malignant disorders (OPMDs), OSCC outcome prediction, and the prediction of the malignant transformation of OPMDs. TNF-α, IL-1β, IL-6 IL-8, LDH, and MMP-9 were the most studied, with almost all studies reporting high sensitivity and specificity values. TNF-α, IL-1β, IL-6 IL-8, LDH, and MMP-9 are the most promising salivary biomarkers. However, more studies with larger cohorts are needed before translating the use of these biomarkers to clinical settings. Full article
(This article belongs to the Special Issue Insights into Oral Squamous Cell Carcinoma)
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