Genetic and methylation status of CDKN2A (p14/p16) and TP53 genes in recurrent respiratory papillomatosis

Chantre-Justino, Mariana; Pires, Ingrid Gonçalves da Veiga; Figueiredo, Marcelo Cardoso; Moreira, Aline dos Santos; Alves, Gilda; Ornellas, Maria Helena

doi:10.1016/j.humpath.2021.11.008

Cited by 5 publications

(4 citation statements)

References 39 publications

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“…Treatment with the demethylating agent 5-aza-2'-deoxycytidine (5-aza-DC) effectively reversed CDKN2A silencing, leading to reduced promoter methylation and increased CDKN2A expression. A previous study[ 37 ] has provided compelling evidence regarding the involvement of epigenetic modifications, specifically high methylation rates, in the development of recurrent respiratory papillomatosis. Notably, the CDKN2A/TP53 pathway appears to be particularly influenced by this epigenetic modulation.…”

Section: Discussionmentioning

confidence: 99%

CDKN2A promoter methylation enhances self-renewal of glioblastoma stem cells and confers resistance to carmustine

Wang,

Xi,

Zhao

et al. 2024

Mol Biol Rep

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Background Glioblastoma, a highly aggressive form of brain cancer, poses significant challenges due to its resistance to therapy and high recurrence rates. This study aimed to investigate the expression and functional implications of CDKN2A, a key tumor suppressor gene, in glioblastoma cells, building upon the existing background of knowledge in this field. Method Quantitative reverse transcription PCR (qRT-PCR) analysis was performed to evaluate CDKN2A expression in U87 glioblastoma cells compared to normal human astrocytes (NHA). CDKN2A expression levels were manipulated using small interfering RNA (siRNA) and CDKN2A overexpression vector. Cell viability assays and carmustine sensitivity tests were conducted to assess the impact of CDKN2A modulation on glioblastoma cell viability and drug response. Sphere formation assays and western blot analysis were performed to investigate the role of CDKN2A in glioblastoma stem cell (GSC) self-renewal and pluripotency marker expression. Additionally, methylation-specific PCR (MSP) assays and demethylation treatment were employed to elucidate the mechanism of CDKN2A downregulation in U87 cells. Result CDKN2A expression was significantly reduced in glioblastoma cells compared to NHA. CDKN2A overexpression resulted in decreased cell viability and enhanced sensitivity to carmustine treatment. CDKN2A inhibition promoted self-renewal capacity and increased pluripotency marker expression in U87 cells. CDKN2A upregulation led to elevated protein levels of p16INK4a, p14ARF, P53, and P21, which are involved in cell cycle regulation. CDKN2A downregulation in U87 cells was associated with high promoter methylation, which was reversed by treatment with a demethylating agent. Conclusion Our findings demonstrate that CDKN2A downregulation in glioblastoma cells is associated with decreased cell viability, enhanced drug resistance, increased self-renewal capacity, and altered expression of pluripotency markers. The observed CDKN2A expression changes are mediated by promoter methylation. These results highlight the potential role of CDKN2A as a therapeutic target and prognostic marker in glioblastoma.

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Section: Discussionmentioning

confidence: 99%

CDKN2A promoter methylation enhances self-renewal of glioblastoma stem cells and confers resistance to carmustine

Wang,

Xi,

Zhao

et al. 2024

Mol Biol Rep

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“…The most crucial tumor-suppressor gene silencing occurs through epigenetic mechanisms ( 32 ). This includes p14, p16/inhibitors of CDK4 ( 33 ), retinoblastoma, cyclin-dependent kinase inhibitor 2 and methylguanine-DNA-methyltransferase, which favor uncontrolled cellular proliferation ( 34 ). In addition, alterations in DNA methylation patterns detected in hematological malignancies are frequently associated with the aberrant activity of enzymes regulating DNA methylation, such as DNMT3A ( 35 ).…”

Section: Epigenetic Mechanisms In Cancer Roles In Carcinogenesis and ...mentioning

confidence: 99%

Modulating epigenetic modifications for cancer therapy (Review)

et al. 2023

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Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non-coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resistance in cancer. The present review describes central epigenetic aberrations during malignant transformation and explains how epidrugs target DNA methylation, histone modifications and ncRNAs. Furthermore, clinical trials focused on evaluating the effect of these epidrugs alone or in combination with other anticancer therapies and other ncRNA-based therapies are discussed. The use of epidrugs promises to be an effective tool for reversing drug resistance in some patients with cancer. Contents1. Introduction 2. Epigenetic mechanisms in cancer, roles in carcinogenesis and therapeutic approaches 3. ncRNAs in epigenetic control 4. Conclusions

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“…The p53 blocker HDM2 is bound by p14arf, which is bound to p53 and triggers p53. A common genetic occurrence in the progression of HNSCCs is a mutation in the gene ARF, which causes the appearance of p14arf ( Chantre-Justino et al, 2022 ). In addition to p53 signaling pathways, secondary factors such as B-cell lymphoma 2 associated X protein (Bax) and Bcl-2 of the apoptotic regulator may be affected ( Rajabi-Moghaddam and Abbaszadeh, 2022 ).…”

Section: Molecular Signaling Cascades Associated With Hnsccmentioning

confidence: 99%

Pharmacological impact of microRNAs in head and neck squamous cell carcinoma: Prevailing insights on molecular pathways, diagnosis, and nanomedicine treatment

Bhattacharjee¹,

Syeda

Rynjah³

et al. 2023

Front. Pharmacol.

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Head and neck squamous cell carcinoma is a disease that most commonly produce tumours from the lining of the epithelial cells of the lips, larynx, nasopharynx, mouth, or oro-pharynx. It is one of the most deadly forms of cancer. About one to two percent of all neo-plasm-related deaths are attributed to head and neck squamous cell carcinoma, which is responsible for about six percent of all cancers. MicroRNAs play a critical role in cell proliferation, differentiation, tumorigenesis, stress response, triggering apoptosis, and other physiological process. MicroRNAs regulate gene expression and provide new diagnostic, prognostic, and therapeutic options for head and neck squamous cell carcinoma. In this work, the role of molecular signaling pathways related to head and neck squamous cell carcinoma is emphasized. We also provide an overview of MicroRNA downregulation and overexpression and its role as a diagnostic and prognostic marker in head and neck squamous cell carcinoma. In recent years, MicroRNA nano-based therapies for head and neck squamous cell carcinoma have been explored. In addition, nanotechnology-based alternatives have been discussed as a promising strategy in exploring therapeutic paradigms aimed at improving the efficacy of conventional cytotoxic chemotherapeutic agents against head and neck squamous cell carcinoma and attenuating their cytotoxicity. This article also provides information on ongoing and recently completed clinical trials for therapies based on nanotechnology.

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Genetic and methylation status of CDKN2A (p14/p16) and TP53 genes in recurrent respiratory papillomatosis

Cited by 5 publications

References 39 publications

CDKN2A promoter methylation enhances self-renewal of glioblastoma stem cells and confers resistance to carmustine

CDKN2A promoter methylation enhances self-renewal of glioblastoma stem cells and confers resistance to carmustine

Modulating epigenetic modifications for cancer therapy (Review)

Pharmacological impact of microRNAs in head and neck squamous cell carcinoma: Prevailing insights on molecular pathways, diagnosis, and nanomedicine treatment

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