Epigenetic regulation in cancer

MedComm, Journal Year: 2024, Volume and Issue: 5(2)

Published: Feb. 1, 2024

Abstract Epigenetic modifications are defined as heritable changes in gene activity that do not involve the underlying DNA sequence. The oncogenic process is driven by accumulation of alterations impact genome's structure and function. Genetic mutations, which directly disrupt sequence, complemented epigenetic modulate expression, thereby facilitating acquisition malignant characteristics. Principals among these shifts methylation histone mark patterns, promote tumor development metastasis. Notably, reversible nature alterations, opposed to permanence genetic changes, positions machinery a prime target discovery novel therapeutics. Our review delves into complexities regulation, exploring its profound effects on initiation, metastatic behavior, metabolic pathways, microenvironment. We place particular emphasis dysregulation at each level modulation, including but limited to, aberrations enzymes responsible for modification, subunit loss or fusions chromatin remodeling complexes, disturbances higher‐order structure. Finally, we also evaluate therapeutic approaches leverage growing understanding dysregulation, offering new avenues cancer treatment.

Language: Английский

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Metal Ion Signaling in Biomedicine

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Complex multicellular organisms are composed of distinct tissues involving specialized cells that can perform specific functions, making such life forms possible. Species defined by their genomes, and differences between individuals within a given species directly result from variations in genetic codes. While alterations give rise to disease-causing acquisitions cell identities, it is now well-established biochemical imbalances also lead cellular dysfunction diseases. Specifically, nongenetic chemical events orchestrate metabolism transcriptional programs govern functional identity. Thus, signaling, which broadly defines the conversion extracellular signals into intracellular changes, contribute acquisition diseased states. Metal ions exhibit unique properties be exploited cell. For instance, metal maintain ionic balance cell, coordinate amino acid residues or nucleobases altering folding function biomolecules, catalyze reactions. metals essential signaling effectors normal physiology disease. Deciphering ion challenging endeavor illuminate pathways targeted for therapeutic intervention. Here, we review key processes where play roles describe how targeting has been instrumental dissecting biochemistry this led development effective strategies.

Language: Английский

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Interplay between genetics and epigenetics in lung fibrosis

The International Journal of Biochemistry & Cell Biology, Journal Year: 2025, Volume and Issue: unknown, P. 106739 - 106739

Published: Jan. 1, 2025

Language: Английский

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Mutant p53 on the Path to Metastasis

Trends in cancer, Journal Year: 2019, Volume and Issue: 6(1), P. 62 - 73

Published: Dec. 16, 2019

Language: Английский

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Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review

Cells, Journal Year: 2020, Volume and Issue: 9(8), P. 1896 - 1896

Published: Aug. 13, 2020

Despite great strides being achieved in improving cancer patients’ outcomes through better therapies and combinatorial treatment, several hurdles still remain due to therapy resistance, recurrence metastasis. Drug resistance culminating relapse continues be associated with fatal disease. The stem cell theory posits that tumors are driven by specialized cells called (CSCs). CSCs a subpopulation of known resistant cause Whilst the debate on whether origins primary tumor rages on, have been further characterized many cancers data illustrating display abilities self-renew, resist enhanced epithelial mesenchymal (EMT) properties, expression ATP-binding cassette (ABC) membrane transporters, activation survival signaling pathways increased immune evasion as well DNA repair mechanisms. also heterogeneity consequential lack specific CSC markers presenting challenge their targeting. In this updated review we revisit within microenvironment (TME) present novel treatment strategies targeting CSCs. These promising include CSCs-specific properties using small molecule inhibitors, immunotherapy, microRNA mediated epigenetic methods niche-microenvironmental factors differentiation. Lastly, recent clinical trials undertaken try turn tide against CSC-associated drug

Language: Английский

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MicroRNAs and Epigenetics Strategies to Reverse Breast Cancer

Cells, Journal Year: 2019, Volume and Issue: 8(10), P. 1214 - 1214

Published: Oct. 8, 2019

Breast cancer is a sporadic disease with genetic and epigenetic components. Genomic instability in breast leads to mutations, copy number variations, rearrangements, while remodeling involves alteration by DNA methylation, histone modification microRNAs (miRNAs) of gene expression profiles. The accrued scientific findings strongly suggest dysregulation pathogenesis though genomic central hallmarks. Being reversible plastic, processes appear more amenable toward therapeutic intervention than the unidirectional alterations. In this review, we discuss reprogramming associated such as shuffling acetylation, miRNAs As part this, illustrate how orchestrates attainment hallmarks which stimulate neoplastic transformation-tumorigenesis-malignancy cascades. reversibility controls promising feature optimize for devising novel approaches, also focus on strategies restoring epistate that favor improved outcome intervention.

Language: Английский

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Machine Learning and Network Analyses Reveal Disease Subtypes of Pancreatic Cancer and their Molecular Characteristics

Scientific Reports, Journal Year: 2020, Volume and Issue: 10(1)

Published: Jan. 27, 2020

Abstract Given that the biological processes governing oncogenesis of pancreatic cancers could present useful therapeutic targets, there is a pressing need to molecularly distinguish between different clinically relevant cancer subtypes. To address this challenge, we used targeted proteomics and other molecular data compiled by The Cancer Genome Atlas reveal tumours can be broadly segregated into two distinct Besides being associated with substantially clinical outcomes, belonging each these subtypes also display notable differences in diverse signalling pathways processes. At proteome level, show less severe subtype are characterised aberrant mTOR signalling, whereas those more disruptions SMAD cell cycle-related We use machine learning algorithms define sets proteins, mRNAs, miRNAs DNA methylation patterns serve as biomarkers accurately differentiate Lastly, confirm relevance identified showing together pattern-recognition infer drug sensitivity lines. Our study shows integrative profiling multiple types enables representation comprehensive enough provide foundation for future strategies.

Language: Английский

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Circulating Tumor Cells as a Tool for Assessing Tumor Heterogeneity

Theranostics, Journal Year: 2019, Volume and Issue: 9(16), P. 4580 - 4594

Published: Jan. 1, 2019

Tumor heterogeneity is the major cause of failure in cancer prognosis and prediction.Accurately detecting for development biomarkers detection clones resistant to therapy one main goals contemporary medicine.Metastases belong natural history cancer.The present review gives an overview on origin tumor heterogeneity.Recent progress has made it possible isolate characterize circulating cells (CTCs), which are drivers disease between primary sites metastatic foci.The most recent methods characterizing CTCs summarized we discuss power CTC profiling analyzing early advanced diseases.

Language: Английский

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Global Regulation of the Histone Mark H3K36me2 Underlies Epithelial Plasticity and Metastatic Progression

Cancer Discovery, Journal Year: 2020, Volume and Issue: 10(6), P. 854 - 871

Published: March 18, 2020

Abstract Epithelial plasticity, reversible modulation of a cell's epithelial and mesenchymal features, is associated with tumor metastasis chemoresistance, leading causes cancer mortality. Although different master transcription factors epigenetic modifiers have been implicated in this process various contexts, the extent to which unifying, generalized mechanism transcriptional regulation underlies plasticity remains largely unknown. Here, through targeted CRISPR/Cas9 screening, we discovered two histone-modifying enzymes involved writing erasing H3K36me2 that act reciprocally regulate epithelial-to-mesenchymal identity, differentiation, metastasis. Using lysine-to-methionine histone mutant directly inhibit H3K36me2, found global mark conserved underlying state contexts. Mechanistically, reprograms enhancers regulators state. Our results thus outline unifying epigenome-scale by specific modification regulates cellular cancer. Significance: contributes no strategies exist for pharmacologically inhibiting process. show mark, universal epigenome-wide transition mesenchymal-to-epithelial carcinoma cells. These offer new strategy targeting This article highlighted In Issue feature, p. 747

Language: Английский

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Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation

Journal of Experimental & Clinical Cancer Research, Journal Year: 2020, Volume and Issue: 39(1)

Published: Oct. 27, 2020

Abstract Hypoxia is the major influence factor in physiological and pathological courses which are mainly mediated by hypoxia-inducible factors (HIFs) response to low oxygen tensions within solid tumors. Under normoxia, HIF signaling pathway inhibited due HIF-α subunits degradation. However, hypoxic conditions, activated stabilized, target genes successively activated, resulting a series of tumour-specific activities. The activation HIFs, including HIF-1α, HIF-2α HIF-3α, subsequently induce downstream leads responses, abnormal processes or metabolites turn affect HIFs stability. Given its functions tumors progression, have been regarded as therapeutic targets for improved treatment efficacy. Epigenetics refers alterations gene expression that stable between cell divisions, sometimes generations, but do not involve changes underlying DNA sequence organism. And with development research, epigenetic regulation has found play an important role tumors, providing accumulating basic clinical evidences tumor treatments. Here, given how little reported about overall association epigenetics, we made more systematic review from perspective hope helping others better understand hypoxia pathway, established potential strategies facilitate studies

Language: Английский

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