Deciphering the epigenetic network in cancer radioresistance

Cabrera-Licona, Ariana; Perez-Añorve, Isidro X.; Flores-Fortis, Mauricio; Moral-Hernández, Oscar Del; Rosa, Claudia H. González-De la; Suárez-Sánchez, Rocío; Chávez-Saldaña, Margarita; Aréchaga-Ocampo, Elena

doi:10.1016/j.radonc.2021.03.012

Cited by 32 publications

(24 citation statements)

References 60 publications

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“…Epigenetic mechanisms such as DNA methylation, histone modification, chromatin remodeling, and non-coding RNAs have a key role in the development of the radiation resistance of cancer cells, as seen in our results. Many epigenetic drugs can revert the radioresistant phenotypes, and clinical trials are currently ongoing in epi-drugs combined with radiotherapy [38,39]. Epigenetic factors have an equally important role in drug resistance as radiation resistance [40][41][42][43].…”

Section: Discussionmentioning

confidence: 99%

EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer

et al. 2021

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EPHA3, a member of the EPH family, is overexpressed in various cancers. We demonstrated previously that EPHA3 is associated with radiation resistance in head and neck cancer via the PTEN/Akt/EMT pathway; the inhibition of EPHA3 significantly enhances the efficacy of radiotherapy in vitro and in vivo. In this study, we investigated the mechanisms of PTEN regulation through EPHA3-related signaling. Increased DNA methyltransferase 1 (DNMT1) and enhancer of zeste homolog 2 (EZH2) levels, along with increased histone H3 lysine 27 trimethylation (H3K27me3) levels, correlated with decreased levels of PTEN in radioresistant head and neck cancer cells. Furthermore, PTEN is regulated in two ways: DNMT1-mediated DNA methylation, and EZH2-mediated histone methylation through EPHA3/C-myc signaling. Our results suggest that EPHA3 could display a novel regulatory mechanism for the epigenetic regulation of PTEN in radioresistant head and neck cancer cells.

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Section: Discussionmentioning

confidence: 99%

EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer

et al. 2021

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“…In addition, the deep relationship between hypoxia and epigenetic also impacts the “Repair” ( 90 ). Indeed, hypoxia-induced epigenetic modulations can directly impact the DDR orchestration, which relies on chromatin remodeling ( 91 , 92 ).…”

Section: Repair: the Versatile Impact Of Hypoxia On Dna Damage Repairmentioning

confidence: 99%

Hypoxia in Solid Tumors: How Low Oxygenation Impacts the “Six Rs” of Radiotherapy

et al. 2021

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Radiotherapy is an important component of cancer treatment, with approximately 50% of all cancer patients receiving radiation therapy during their course of illness. Nevertheless, solid tumors frequently exhibit hypoxic areas, which can hinder therapies efficacy, especially radiotherapy one. Indeed, hypoxia impacts the six parameters governing the radiotherapy response, called the « six Rs of radiation biology » (for Radiosensitivity, Repair, Repopulation, Redistribution, Reoxygenation, and Reactivation of anti-tumor immune response), by inducing pleiotropic cellular adaptions, such as cell metabolism rewiring, epigenetic landscape remodeling, and cell death weakening, with significant clinical repercussions. In this review, according to the six Rs, we detail how hypoxia, and associated mechanisms and pathways, impact the radiotherapy response of solid tumors and the resulting clinical implications. We finally illustrate it in hypoxic endocrine cancers through a focus on anaplastic thyroid carcinomas.

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“…New sequencing methodologies allow to study epigenomics with an unprecedented resolutive power, including reduced-representation bisulfite sequencing (RRBS) and whole-genome bisulfite sequencing (WGBS), analyzing full genomes [154]. This has significant implications in many areas, such as ecology [155], environmental pollution including radiation [156,157], with relevant implications for cancer radioresistance [158] and health [135,138], as well neuropsychiatric disorders [159]. Besides, it has been found that mechanotransduction is involved in mechanical regulation of transcription and the epigenome, having a key role in cancer progression [160].…”

Section: Epigenomicsmentioning

confidence: 99%

Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing – Review

et al. 2021

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Recent developments have revolutionized the study of biomolecules. Among them are molecular markers, amplification and sequencing of nucleic acids. The latter is classified into three generations. The first allows to sequence small DNA fragments. The second one increases throughput, reducing turnaround and pricing, and is therefore more convenient to sequence full genomes and transcriptomes. The third generation is currently pushing technology to its limits, being able to sequence single molecules, without previous amplification, which was previously impossible. Besides, this represents a new revolution, allowing researchers to directly sequence RNA without previous retrotranscription. These technologies are having a significant impact on different areas, such as medicine, agronomy, ecology and biotechnology. Additionally, the study of biomolecules is revealing interesting evolutionary information. That includes deciphering what makes us human, including phenomena like non-coding RNA expansion. All this is redefining the concept of gene and transcript. Basic analyses and applications are now facilitated with new genome editing tools, such as CRISPR. All these developments, in general, and nucleic-acid sequencing, in particular, are opening a new exciting era of biomolecule analyses and applications, including personalized medicine, and diagnosis and prevention of diseases for humans and other animals.

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Deciphering the epigenetic network in cancer radioresistance

Cited by 32 publications

References 60 publications

EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer

EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer

Hypoxia in Solid Tumors: How Low Oxygenation Impacts the “Six Rs” of Radiotherapy

Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing – Review

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