Methylation synthetic lethality: Exploiting selective drug targets for cancer therapy DOI
B. Hilda Ye,

Di‐Fei Li,

Xinyun Li

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 597, P. 217010 - 217010

Published: June 6, 2024

Language: Английский

RNA m6A regulates transcription via DNA demethylation and chromatin accessibility DOI
Shuang Deng, Jialiang Zhang, Jiachun Su

et al.

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(9), P. 1427 - 1437

Published: Sept. 1, 2022

Language: Английский

Citations

101

Methylation across the central dogma in health and diseases: new therapeutic strategies DOI Creative Commons
Ruochen Liu, Erhu Zhao,

Huijuan Yu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 24, 2023

The proper transfer of genetic information from DNA to RNA protein is essential for cell-fate control, development, and health. Methylation DNA, RNAs, histones, non-histone proteins a reversible post-synthesis modification that finetunes gene expression function in diverse physiological processes. Aberrant methylation caused by mutations or environmental stimuli promotes various diseases accelerates aging, necessitating the development therapies correct disease-driver imbalance. In this Review, we summarize operating system across central dogma, which includes writers, erasers, readers, reader-independent outputs. We then discuss how dysregulation contributes neurological disorders, cancer, aging. Current small-molecule compounds target modifiers show modest success certain cancers. methylome-wide action lack specificity lead undesirable biological effects cytotoxicity, limiting their therapeutic application, especially with monogenic cause different directions changes. Emerging tools capable site-specific manipulation hold great promise solve dilemma. With refinement delivery vehicles, these new are well positioned advance basic research clinical translation field.

Language: Английский

Citations

55

Epigenetic regulation of diverse cell death modalities in cancer: a focus on pyroptosis, ferroptosis, cuproptosis, and disulfidptosis DOI Creative Commons

Shimeng Zhou,

Junlan Liu, Andi Wan

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: April 23, 2024

Abstract Tumor is a local tissue hyperplasia resulted from cancerous transformation of normal cells under the action various physical, chemical and biological factors. The exploration tumorigenesis mechanism crucial for early prevention treatment tumors. Epigenetic modification common important in cells, including DNA methylation, histone modification, non-coding RNA m6A modification. mode cell death programmed by death-related genes; however, recent researches have revealed some new modes death, pyroptosis, ferroptosis, cuproptosis disulfidptosis. regulation deaths mainly involved key proteins affects up-regulating or down-regulating expression levels proteins. This study aims to investigate epigenetic modifications regulating disulfidptosis tumor explore possible triggering factors development microscopic point view, provide potential targets therapy perspective antitumor drugs combination therapies.

Language: Английский

Citations

30

Multimodal analysis of cfDNA methylomes for early detecting esophageal squamous cell carcinoma and precancerous lesions DOI Creative Commons
Jiaqi Liu,

Lijun Dai,

Qiang Wang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 2, 2024

Detecting early-stage esophageal squamous cell carcinoma (ESCC) and precancerous lesions is critical for improving survival. Here, we conduct whole-genome bisulfite sequencing (WGBS) on 460 cfDNA samples from patients with non-metastatic ESCC or matched healthy controls. We develop an expanded multimodal analysis (EMMA) framework to simultaneously identify methylation, copy number variants (CNVs), fragmentation markers in WGBS data. methylation are the earliest most sensitive, detectable 70% of ESCCs 50% lesions, associated molecular subtypes tumor microenvironments. CNVs features show high specificity but linked late-stage disease. EMMA significantly improves detection rates, increasing AUCs 0.90 0.99, detects 87% 62% >95% validation cohorts. Our findings demonstrate potential methylome early monitoring characteristics ESCC.

Language: Английский

Citations

11

NMR and MS reveal characteristic metabolome atlas and optimize esophageal squamous cell carcinoma early detection DOI Creative Commons
Yan Zhao,

Changchun Ma,

Rongzhi Cai

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 19, 2024

Metabolic changes precede malignant histology. However, it remains unclear whether detectable characteristic metabolome exists in esophageal squamous cell carcinoma (ESCC) tissues and biofluids for early diagnosis. Here, we conduct NMR- MS-based metabolomics on 1,153 matched ESCC tissues, normal mucosae, pre- one-week post-operative sera urines from 560 participants across three hospitals, with machine learning WGCNA. Aberrations 'alanine, aspartate glutamate metabolism' proved to be prevalent throughout the evolution, consistently identified by NMR MS, reflected 16 serum 10 urine metabolic signatures both discovery validation sets. NMR-based simplified panels of any five or metabolites outperform clinical serological tumor markers (AUC = 0.984 0.930, respectively), are effective distinguishing early-stage test set (serum accuracy 0.994, 0.879). Collectively, biofluid screening can reveal events feasible detection (ChiCTR2300073613).

Language: Английский

Citations

10

Methylomics and cancer: the current state of methylation profiling and marker development for clinical care DOI Creative Commons
Chengyin Liu,

Han Tang,

Nana Hu

et al.

Cancer Cell International, Journal Year: 2023, Volume and Issue: 23(1)

Published: Oct. 16, 2023

Abstract Epigenetic modifications have long been recognized as an essential level in transcriptional regulation linking behavior and environmental conditions or stimuli with biological processes disease development. Among them, methylation is the most abundant of these reversible epigenetic marks, predominantly occurring on DNA, RNA, histones. Methylation modification intimately involved regulating gene transcription cell differentiation, while aberrant status has linked cancer development several malignancies. Early detection precise restoration dysregulated form basis for epigenetics-based therapeutic strategies. In this review, we summarize current basic understanding mechanisms responsible cover cutting-edge research techniques detecting across genome transcriptome. We then explore recent advances clinical diagnostic applications markers various cancers address state future prospects therapies different diseases, especially comparing pharmacological methylase/demethylase inhibitors CRISPRoff/on editing systems. This review thus provides a resource emerging role cancer, use methylation-based biomarkers detection, novel methylation-targeted drugs.

Language: Английский

Citations

20

Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis DOI Creative Commons
Cong Chen, Jie Wang,

Shan Zhang

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 76, P. 103321 - 103321

Published: Aug. 19, 2024

Cell death constitutes a critical component of the pathophysiology cardiovascular diseases. A growing array non-apoptotic forms regulated cell (RCD)-such as necroptosis, ferroptosis, pyroptosis, and cuproptosis-has been identified is intimately linked to various conditions. These RCD are governed by genetically programmed mechanisms within cell, with epigenetic modifications being common crucial regulatory method. Such include DNA methylation, RNA histone acetylation, non-coding RNAs. This review recaps roles modifications, RNAs in diseases, well which regulate key proteins involved death. Furthermore, we systematically catalog existing pharmacological agents targeting novel their action article aims underscore pivotal role precisely regulating specific pathways thus offering potential new therapeutic avenues that may prove more effective safer than traditional treatments.

Language: Английский

Citations

7

Methylation in cornea and corneal diseases: a systematic review DOI Creative Commons

Yutong Xia,

Kuangqi Chen,

Qianjie Yang

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: April 8, 2024

Abstract Corneal diseases are among the primary causes of blindness and vision loss worldwide. However, pathogenesis corneal remains elusive, diagnostic therapeutic tools limited. Thus, identifying new targets for diagnosis treatment has gained great interest. Methylation, a type epigenetic modification, modulates various cellular processes at both nucleic acid protein levels. Growing evidence shows that methylation is key regulator in diseases, including inflammation, fibrosis, neovascularization, making it an attractive potential target. In this review, we discuss major alterations demethylation DNA, RNA, levels how these dynamics contribute to diseases. Also, provide insights into biomarkers may improve

Language: Английский

Citations

4

Zinc finger protein ZC3H18 is abnormally expressed in esophageal cancer tissues and facilitates the proliferation of esophageal cancer cells DOI Creative Commons
Yujin Zhang,

Yilong Wan,

Jia Liu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 25, 2025

Esophageal cancer presents significant challenges due to the limited efficacy and severe side effects associated with conventional treatments. The identification of epigenetic regulatory molecules that are aberrantly expressed in tumors is crucial for elucidating mechanisms underlying development progression esophageal cancer. We performed high-throughput methylation level analysis on cancerous adjacent tissues from 25 patients, identifying differentially methylated gene ZC3H18 utilizing Bismark software data TCGA. cell lines knockdown were used validate biological role tumorigenesis vitro vivo. Eukaryotic transcriptome sequencing was conducted investigate potential function. identified 30 genes exhibiting differences between non-cancerous patients. Subsequent TCGA database revealed tumor closely patient prognosis. Examination tissue samples demonstrated overexpression protein, which positively correlated adverse prognosis indicators, including differentiation, stage, invasion depth. significantly inhibited cellular proliferation, migration, invasion, damage repair. Additionally, promoted growth expression various cytokeratins reduced following knockdown. multiple keratins co-localized tissue. exhibits differential unfavorable plays a critical regulation functions within tumors.

Language: Английский

Citations

0

Integrative genome-wide aberrant DNA methylation and transcriptome analysis identifies diagnostic markers for colorectal cancer DOI

Hengyang Shen,

Zhenling Wang, Yang Chen

et al.

Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Language: Английский

Citations

0