Metazoan organisms are dependent on a continuous supply of O2 for survival. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in dev...

Regulation of Oxygen Homeostasis by Hypoxia-Inducible Factor 1

Background: N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1-methyladenosine (m1A) are the main RNA methylation modifications involved in the progression of cancer. However, it is still unclear whether m6A/m5C/m1A-related long non-coding RNAs (lncRNAs) affect the prognosis of head and neck squamous cell carcinoma (HNSCC). Methods: We summarized 52 m6A/m5C/m1A-related genes, downloaded 44 normal samples and 501 HNSCC tumor samples with RNA-seq data and clinical information from The Cancer Genome Altas (TCGA) database, and then searched for m6A/m5C/m1A-related genes co-expressed lncRNAs. We adopt the least absolute shrinkage and selection operator (LASSO) Cox regression to obtain m6A/m5C/m1A-related lncRNAs to construct a prognostic signature of HNSCC. Results: This prognostic signature is based on six m6A/m5C/m1A-related lncRNAs (AL035587.1, AC009121.3, AF131215.5, FMR1-IT1, AC106820.5, PTOV1-AS2). It was found that the high-risk subgroup has worse overall survival (OS) than the low-risk subgroup. Moreover, the results showed that most immune checkpoint genes were significantly different between the two risk groups (P < 0.05). Immunity microenvironment analysis showed that the contents of NK cell resting, macrophages M2, and neutrophils in samples of low-risk group were significantly lower than those of high-risk group (P < 0.05), while the contents of B cells navie, plasma cells, and T cells regulatory (Tregs) were on the contrary (P < 0.05). In addition, patients with high TMB had the worse OS than those with low TMB. Conclusion: Our study elucidated how m6A/m5C/m1A-related lncRNAs are related to the prognosis, immune microenvironment, and TMB of HNSCC. In the future, these m6A/m5C/m1A-related lncRNAs may become a new choice for immunotherapy of HNSCC.

The Prognostic Value and Immune Landscapes of a m6A/m5C/m1A-Related LncRNAs Signature in Head and Neck Squamous Cell Carcinoma

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924639

Chorioallantoic membrane tumor models highlight the effects of cisplatin compounds in oral carcinoma treatment

Head and neck squamous cell carcinomas (HNSCC) are among the ten most frequent types of cancer worldwide and, despite all efforts, are still diagnosed at late stages and show poor overall survival. Furthermore, HNSCC patients often experience relapses and the development of second primary tumors, as a consequence of the field cancerization process. Therefore, a better comprehension of the molecular mechanisms involved in HNSCC development and progression may enable diagnosis anticipation and provide valuable tools for prediction of prognosis and response to therapy. However, the different biological behavior of these tumors depending on the affected anatomical site and risk factor exposure, as well as the high genetic heterogeneity observed in HNSCC are major obstacles in this pursue. In this context, epigenetic alterations have been shown to be common in HNSCC, to discriminate the tumor anatomical subsites, to be responsive to risk factor exposure, and show promising results in biomarker development. Based on this, this review brings together the current knowledge on alterations of DNA methylation and microRNA expression in HNSCC natural history, focusing on how they contribute to each step of the process and on their applicability as biomarkers of exposure, HNSCC development, progression, and response to therapy.

Head and Neck Cancers Are Not Alike When Tarred with the Same Brush: An Epigenetic Perspective from the Cancerization Field to Prognosis.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly heterogeneous group of tumors characterized by an incidence of 650,000 new cases and 350,000 deaths per year worldwide and a male to female ratio of 3:1. The main risk factors are alcohol and tobacco consumption and Human Papillomavirus (HPV) infections. HNSCC cases are divided into two subgroups, the HPV-negative (HPV−) and the HPV-positive (HPV+) which have different clinicopathological and molecular profiles. However, patients are still treated with the same therapeutic regimens. It is thus of utmost importance to characterize the molecular mechanisms underlying these differences to find new biomarkers and novel therapeutic targets towards personalized therapies. Epigenetic alterations are a hallmark of cancer and can be exploited as both promising biomarkers and potential new targets. E6 and E7 HPV oncoviral proteins besides targeting p53 and pRb, impair the expression and the activity of several epigenetic regulators. While alterations in DNA methylation patterns have been well described in HPV+ and HPV− HNSCC, accurate histone post-translational modifications (hPTMs) characterization is still missing. Herein, we aim to provide an updated overview on the impact of HPV on the hPTMs landscape in HNSCC. Moreover, we will also discuss the sex and gender bias in HNSCC and how the epigenetic machinery could be involved in this process, and the importance of taking into account sex and/or gender also in this field.

/pdf/high-risk-human-papillomavirus-in-hnscc-present-and-future-2rc4q8fw.pdf

High Risk-Human Papillomavirus in HNSCC: Present and Future Challenges for Epigenetic Therapies

Head and neck squamous carcinoma (HNSCC) constitutes the sixth most prevalent cancer worldwide. The molecular pathogenesis of HNSCC includes disorders in cell cycle, intercellular signaling, proliferation, squamous cell differentiation and apoptosis. In addition to the genetic mutations, changes in HNSCC are also characterized by the accumulation of epigenetic alterations such as DNA methylation, histone modifications, non-coding RNA activity and RNA methylation. In fact, some of them may promote cancer formation and progression by controlling the gene expression machinery, hence, they could be used as biomarkers in the clinical surveillance of HNSCC or as targets for therapeutic strategies. In this review, we focus on the current knowledge regarding epigenetic modifications observed in HNSCC and its predictive value for cancer development.

https://www.mdpi.com/2075-4418/11/1/34/pdf

Head and Neck Squamous Cell Carcinoma: Epigenetic Landscape.

RNA methylation at the nitrogen sixth of adenosine (m6A, N6-methyladenosine) is the most abundant RNA modification which plays a crucial role in all RNA metabolic aspects. Recently, m6A modification has been assigned to mediate the biological processes of cancer cells, but their significance in HNSCC development is still poorly described. Thus, the main aim of this study was to globally quantify m6A modification by the mass spectrometry approach and determine the mRNA expression level of selected m6A RNA methyltransferase (METTL3), demethylase (FTO), and m6A readers (YTHDF2, YTHDC2) in 45 HNSCC patients and 4 cell lines (FaDu, Detroit 562, A-253 and SCC-15) using qPCR. In the results, we have not observed differences in the global amount of m6A modification and the mRNA level of the selected genes between the cancerous and paired-matched histopathologically unchanged tissues from 45 HNSCC patients. However, we have found a positive correlation between selected RNA methylation machinery genes expression and m6A abundance on total RNA and characterized the transcript level of those genes in the HNSCC cell lines. Moreover, the lack of global m6A differences between cancerous and histopathologically unchanged tissues suggests that m6A alterations in specific RNA sites may specifically influence HNSCC tumorigenesis.

https://www.mdpi.com/2218-273X/11/6/908/pdf

The m6A RNA Modification Quantity and mRNA Expression Level of RNA Methylation-Related Genes in Head and Neck Squamous Cell Carcinoma Cell Lines and Patients.

Disturbances in partial pressure of oxygen control play a key role in the pathogenesis of many diseases, including cancer. Solid tumor cells are particularly susceptible to hypoxia as a result of uncontrolled tumor growth and low, chaotic vascularization in the neoplastic region. Reduced oxygen pressure in cancer cells is associated with a more aggressive phenotype and an increased metastatic potential. In conditions of insufficient oxygen, tumors adapt to the prevailing conditions by activating genes responsible for cell survival, neovascularization and apoptosis inhibition. In head and neck cancers (HNC), conditions of hypoxia are often correlated with alterations in cellular metabolism and immune response to radio- and chemotherapy.

/pdf/znaczenie-hipoksji-w-nowotworach-glowy-i-szyi-3bxlm18btp.pdf

Znaczenie hipoksji w nowotworach głowy i szyi

Wprowadzenie technik edycji genomu jako podstawowego narzędzia w badaniach naukowych wywołało znaczny postęp w naukach biologicznych, medycznych oraz pozwoliło zrozumieć patofizjologię wielu chorób. Jedną z najnowocześniejszych metod wprowadzania specyficznych zmian w genomie jest obecnie technologia CRISPR/Cas9, która poprzez insercję, delecję lub zamianę nukleotydów w sekwencji DNA prowadzi do inaktywacji genów docelowych, nabycia nowych cech genetycznych lub korekty niepożądanych mutacji. Ponadto, technologia CRISPR/Cas9 pozwala na tworzenie modeli in vitro i in vivo wielu chorób, a następnie dokładne badanie mechanizmów ich powstawania. Obecnie prowadzonych jest wiele badań w dziedzinie onkologii wykorzystujących technikę CRISPR/Cas9, a niniejsza praca jest ich zwięzłym podsumowaniem.

/pdf/zastosowanie-technologii-crispr-cas9-w-leczeniu-nowotworow-1hn3288y.pdf

Zastosowanie technologii CRISPR/Cas9 w leczeniu nowotworów

Head and neck cancer (HNC) is the sixth most prevalent cancer worldwide, representing more than a half million of the new cases every year. Due to high genetic and histologic diversity of head and neck cancers, their molecular pathogenesis is based on complex process including disorders driven not only by accumulation of genetic alterations, but also changes in epigenetic landscape. The epigenetic variations in HNC include DNA methylation, histone modifications, non-coding RNA activity and RNA methylation. Some of the epigenetic alterations promote cancer formation and progression by controlling the expression machinery. Consequently, those modifications can be used as biomarkers for clinical detection and surveillance of cancer and will reveal new therapeutic opportunities for cancer patients.

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Kamila Romanowska

Papers

Head and Neck Squamous Cell Carcinoma: Epigenetic Landscape.

The m6A RNA Modification Quantity and mRNA Expression Level of RNA Methylation-Related Genes in Head and Neck Squamous Cell Carcinoma Cell Lines and Patients.

Znaczenie hipoksji w nowotworach głowy i szyi

Zastosowanie technologii CRISPR/Cas9 w leczeniu nowotworów

Epigenetyka jako obiecująca dziedzina nauki w walce z nowotworami głowy i szyi