Investigation of PTEN promoter methylation in ameloblastoma

Lapthanasupkul, Puangwan; Klongnoi, Boworn; Mutirangura, Apiwat; Kitkumthorn, Nakarin

doi:10.4317/medoral.23498

Cited by 14 publications

(18 citation statements)

References 24 publications

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“…MSH2 and MSH6 showed a negative correlation between the methylation status and their respective immunohistochemistry expression, similar to that observed in sporadic colorectal cancer (Malhotra et al., 2014). However, the same correlation was not observed with the MSH3 analysis, suggesting that other mechanisms might be involved in this gene regulation as were reported with the PTEN gene in ameloblastoma (Lapthanasupkul et al., 2020). The current sample size could be a limitation in our study what could explain the lack of the statistical significance detected for MSH3.…”

Section: Discussionsupporting

confidence: 67%

“…analysis, suggesting that other mechanisms might be involved in this gene regulation as were reported with the PTEN gene in ameloblastoma (Lapthanasupkul et al, 2020). The current sample size could be a limitation in our study what could explain the lack of the statistical significance detected for MSH3.…”

Section: Muts Genes Methylation Status and Muts Immunohistochemistry ...mentioning

confidence: 67%

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DNA methylation status of MutS genes in ameloblastoma

et al. 2021

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Objectives: Ameloblastoma is an odontogenic epithelial tumour with a low expression of mismatch repair system components. We aimed to investigate the methylation status of the genes MSH2, MSH3 and MSH6 (MutS group) in conventional ameloblastomas. Materials and Methods:The ameloblastoma and dental follicle samples (n = 10 each) were collected from 20 different patients. Each ameloblastoma sample was sectioned into two fragments: one was paraffin-embedded while the other one, likewise the dental follicle samples, was fixed in RNAlater and frozen at −196°C. All frozen samples were investigated for the MutS genes methylation levels, using the enzymatic restriction digestion and quantitative real-time PCR (qPCR) assay. The ameloblastoma paraffin-embedded samples were submitted to immunohistochemical reactions for MutS proteins detection and digitally quantification. Correlation analyses were performed between the immunohistochemical results and the respective gene methylation percentage.Results: There are no significant differences between the MutS genes methylation levels in the ameloblastoma and the dental follicle. However, a strong negative correlation was found between MSH2 and MSH6 gene methylation status and their respective proteins expressions evaluated by immunohistochemistry. Conclusion:Our results show that the genes methylations is in part responsible for decreasing the expression of MSH2 and MSH6 genes in ameloblastoma.

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Section: Discussionsupporting

confidence: 67%

Section: Muts Genes Methylation Status and Muts Immunohistochemistry ...mentioning

confidence: 67%

DNA methylation status of MutS genes in ameloblastoma

et al. 2021

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“…Finally, we identified some regulatory pairs with prognostic significance in several cancers. Moreover, studies have reported that differential expression or methylation is highly related with tumorigenesis through regulating gene expression (69)(70)(71)(72). Our study identified miRNAs/probes that were differentially expressed/methylated between tumor and normal samples, indicating their potential association with tumorigenesis.…”

Section: Discussionmentioning

confidence: 63%

Comprehensive Analysis of Expression Regulation for RNA m6A Regulators With Clinical Significance in Human Cancers

et al. 2021

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BackgroundN6-methyladenosine (m6A), the most abundant chemical modification on eukaryotic messenger RNA (mRNA), is modulated by three class of regulators namely “writers,” “erasers,” and “readers.” Increasing studies have shown that aberrant expression of m6A regulators plays broad roles in tumorigenesis and progression. However, it is largely unknown regarding the expression regulation for RNA m6A regulators in human cancers.ResultsHere we characterized the expression profiles of RNA m6A regulators in 13 cancer types with The Cancer Genome Atlas (TCGA) data. We showed that METTL14, FTO, and ALKBH5 were down-regulated in most cancers, whereas YTHDF1 and IGF2BP3 were up-regulated in 12 cancer types except for thyroid carcinoma (THCA). Survival analysis further revealed that low expression of several m6A regulators displayed longer overall survival times. Then, we analyzed microRNA (miRNA)-regulated and DNA methylation-regulated expression changes of m6A regulators in pan-cancer. In total, we identified 158 miRNAs and 58 DNA methylation probes (DMPs) involved in expression regulation for RNA m6A regulators. Furthermore, we assessed the survival significance of those regulatory pairs. Among them, 10 miRNAs and 7 DMPs may promote cancer initiation and progression; conversely, 3 miRNA/mRNA pairs in kidney renal clear cell carcinoma (KIRC) may exert tumor-suppressor function. These findings are indicative of their potential prognostic values. Finally, we validated two of those miRNA/mRNA pairs (hsa-miR-1307-3p/METTL14 and hsa-miR-204-5p/IGF2BP3) that could serve a critical role for potential clinical application in KIRC patients.ConclusionsOur findings highlighted the importance of upstream regulation (miRNA and DNA methylation) governing m6A regulators’ expression in pan-cancer. As a result, we identified several informative regulatory pairs for prognostic stratification. Thus, our study provides new insights into molecular mechanisms of m6A modification in human cancers.

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“… 27 PTEN acts as a tumor suppressor gene and inactivation of PTEN has been reported in various types of cancers. 28 In order to verify the effect of PTEN, the shRNA-PTEN was transfected into the cells with low expression of miR-130a, and the proliferation and migration of SCC-4 cells were significantly increased after downregulating PTEN at the same time, indicating that downregulating PTEN could reverse the inhibition of miR-130a on the proliferation and migration of SCC-4 cells. PTEN expression was seen to be downregulated in OSCC cells.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of MicroRNA-130a Inhibits Oral Squamous Cell Carcinoma Proliferation and Metastasis via the Hippo-YAP Pathway

Yan¹,

Hu²,

Zhang³

et al. 2021

CMAR

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Introduction Oral squamous cell carcinoma (OSCC) means oral epithelial cell injury caused by multiple genetic mutations of the cells. Dysregulation of microRNAs (miRs) can disrupt the progression of OSCC. This study explored the mechanism of miR-130a in OSCC progression. Methods miR-130a expression in OSCC cell lines was analyzed. Functional assays were utilized to test the alterations of OSCC cell proliferation, apoptosis and epithelial–mesenchymal transition (EMT) with downregulated miR-130a, shRNA-PTEN or/and YAP inhibitor verteporfin. Then, dual-luciferase reporter gene assay was performed to clarify the targeting relation between miR-130a and PTEN. After that, Hippo-YAP pathway-related protein levels were tested. Moreover, xenograft transplantation was applied to confirm the in vitro experiments. Results Highly expressed miR-130a was observed in OSCC cell lines. Silenced miR-130a reduced OSCC proliferation, metastasis, invasion and EMT while propelled apoptosis. Furthermore, miR-130a targeted PTEN to promote the OSCC progression. Downregulation of PTEN reversed the inhibition of silencing miR-130a on proliferation and migration of SCC-4 cells. miR-130a targeted PTEN to inactivate the Hippo-YAP axis. OSCC progression was notably promoted by a combination of YAP inhibitor verteporfin and miR-130a inhibitor. Additionally, silenced miR-130a inhibited OSCC progression in vivo. Discussion Silencing miR-130a inhibited OSCC progression by targeting PTEN and activating the Hippo-YAP axis. This investigation may provide novel insight for OSCC treatment.

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Investigation of PTEN promoter methylation in ameloblastoma

Cited by 14 publications

References 24 publications

DNA methylation status of MutS genes in ameloblastoma

DNA methylation status of MutS genes in ameloblastoma

Comprehensive Analysis of Expression Regulation for RNA m6A Regulators With Clinical Significance in Human Cancers

Downregulation of MicroRNA-130a Inhibits Oral Squamous Cell Carcinoma Proliferation and Metastasis via the Hippo-YAP Pathway

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