Detecting Early-Stage Oral Cancer from Clinically Diagnosed Oral Potentially Malignant Disorders by DNA Methylation Profile

Mori, Kazuki; Hamada, Tomofumi; Beppu, Mahiro; Tsuchihashi, Hiroki; Goto, Yu‐ichi; Kume, K.; Hara, Hiroshi; Nishi, Keitaro; Mishima, Yumiko; Sugiura, Tetsuro

doi:10.3390/cancers14112646

Cited by 4 publications

(3 citation statements)

References 37 publications

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“…Mori et al. also found a combination of six genes, including RARB could distinguish oral cancer from clinically diagnosed oral potentially malignant disorders with high diagnostic performance [ 17 ]. In addition, polymethoxyflavones extracted from citrus inhibited gastric cancer cell proliferation through triggering apoptosis by upregulating RARB in vitro and in vivo [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic regulation of RARB overcomes the radio-resistance of colorectal carcinoma cells via cancer stem cells

Shu

Lan²,

et al. 2022

Journal of Radiation Research

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Cancer stem cells (CSCs) are able to survive after cancer therapies, leading to cancer progression and recurrence in colorectal carcinoma (CRC). Therapies targeting CSCs are believed to be promising strategies for efficiently eradicating cancers. This study was to investigate that how retinoic acid receptor beta (RARB) affected the biological characteristics of CSCs and radio-resistance in CRC and the epigenetic mechanism. The sensitivity of CSCs isolated from HCT116 cells to radiotherapy was reduced compared with the parental cells. Using database querying, we found that RARB was one of the most significantly downregulated gene in radio-resistant cells in CRC. Also, RARB was poorly expressed in our isolated CSCs, and overexpression of RARB inhibited the properties of CSCs and enhanced radiotherapy sensitivity. Mechanistically, the methylation of RARB was higher in CSCs compared with HCT116 cells, which was significantly reduced after the application of DNA methylation inhibitor 5-azacytidine (5-azaC). DNA methyltransferases (DNMT1) was found to be recruited into the RARB promoter. 5-AzaC treatment inhibited DNMT1 activity and improved radiotherapy sensitivity by promoting RARB expression. Our results imply that inhibition of DNMT1 can display a new mechanism for the epigenetic mediation of RARB in radio-resistant CRC.

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Section: Discussionmentioning

confidence: 99%

Epigenetic regulation of RARB overcomes the radio-resistance of colorectal carcinoma cells via cancer stem cells

Shu

Lan²,

et al. 2022

Journal of Radiation Research

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“…The detection of OSCC in the early stages is difficult, as most of the cases are asymptomatic and, by clinical examination, look similar to PMOLs such as leukoplakia, erythroplakia or OLP [ 109 , 110 ]. Moreover, the distinction between different types of PMOLs is difficult, and from a clinical point of view, the majority of cases will have an imprecise diagnosis [ 111 ].…”

Section: Difficulties Associated With the Early Diagnosis Of Osccmentioning

confidence: 99%

The Use of Salivary Levels of Matrix Metalloproteinases as an Adjuvant Method in the Early Diagnosis of Oral Squamous Cell Carcinoma: A Narrative Literature Review

Monea

Pop

2022

CIMB

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Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with increased mortality, in which the early diagnosis is the most important step in increasing patients’ survival rate. Extensive research has evaluated the role of saliva as a source of diagnostic biomarkers, among which matrix metalloproteinases (MMPs) have shown a valuable potential for detecting even early stages of OSCC. The aim of this review was to present recent clinical data regarding the significance of salivary MMPs in the detection of early malignant transformation of the oral mucosa. A narrative review was conducted on articles published in PubMed, Cochrane Library, Web of Science, EBSCO and SciELO databases, using specific terms. Our search revealed that MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-12 and MMP-13 had significantly higher levels in saliva from patients with OSCC compared to controls. However, the strength of evidence is limited, as most information regarding their use as adjuvant diagnostic tools for OSCC comes from studies with a low number of participants, variable methodologies for saliva sampling and diagnostic assays, and insufficient adjustment for all covariates. MMP-1, MMP-3 and MMP-9 were considered the most promising candidates for salivary diagnosis of OSCC, but larger studies are needed in order to validate their clinical application.

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“…DNA methylation, a prevalent epigenetic modification that governs gene expression patterns, cell type-specific genome stability and embryonic development in eukaryotes [ 9 ], has been closely linked to oral cancer progression [ 10 , 11 ]. Changes in DNA methylation patterns associated with carcinogenesis progress gradually with cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

DNMT1-targeting remodeling global DNA hypomethylation for enhanced tumor suppression and circumvented toxicity in oral squamous cell carcinoma

Liu,

Sun,

Yang

et al. 2024

Mol Cancer

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Background The faithful maintenance of DNA methylation homeostasis indispensably requires DNA methyltransferase 1 (DNMT1) in cancer progression. We previously identified DNMT1 as a potential candidate target for oral squamous cell carcinoma (OSCC). However, how the DNMT1- associated global DNA methylation is exploited to regulate OSCC remains unclear. Methods The shRNA-specific DNMT1 knockdown was employed to target DNMT1 on oral cancer cells in vitro, as was the use of DNMT1 inhibitors. A xenografted OSCC mouse model was established to determine the effect on tumor suppression. High-throughput microarrays of DNA methylation, bulk and single-cell RNA sequencing analysis, multiplex immunohistochemistry, functional sphere formation and protein immunoblotting were utilized to explore the molecular mechanism involved. Analysis of human samples revealed associations between DNMT1 expression, global DNA methylation and collaborative molecular signaling with oral malignant transformation. Results We investigated DNMT1 expression boosted steadily during oral malignant transformation in human samples, and its inhibition considerably minimized the tumorigenicity in vitro and in a xenografted OSCC model. DNMT1 overexpression was accompanied by the accumulation of cancer-specific DNA hypomethylation during oral carcinogenesis; conversely, DNMT1 knockdown caused atypically extensive genome-wide DNA hypomethylation in cancer cells and xenografted tumors. This novel DNMT1-remodeled DNA hypomethylation pattern hampered the dual activation of PI3K-AKT and CDK2-Rb and inactivated GSK3β collaboratively. When treating OSCC mice, targeting DNMT1 achieved greater anticancer efficacy than the PI3K inhibitor, and reduced the toxicity of blood glucose changes caused by the PI3K inhibitor or combination of PI3K and CDK inhibitors as well as adverse insulin feedback. Conclusions Targeting DNMT1 remodels a novel global DNA hypomethylation pattern to facilitate anticancer efficacy and minimize potential toxic effects via balanced signaling synergia. Our study suggests DNMT1 is a crucial gatekeeper regarding OSCC destiny and treatment outcome.

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Detecting Early-Stage Oral Cancer from Clinically Diagnosed Oral Potentially Malignant Disorders by DNA Methylation Profile

Cited by 4 publications

References 37 publications

Epigenetic regulation of RARB overcomes the radio-resistance of colorectal carcinoma cells via cancer stem cells

Epigenetic regulation of RARB overcomes the radio-resistance of colorectal carcinoma cells via cancer stem cells

The Use of Salivary Levels of Matrix Metalloproteinases as an Adjuvant Method in the Early Diagnosis of Oral Squamous Cell Carcinoma: A Narrative Literature Review

DNMT1-targeting remodeling global DNA hypomethylation for enhanced tumor suppression and circumvented toxicity in oral squamous cell carcinoma

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