Homocysteine facilitates endoplasmic reticulum stress and apoptosis of hepatocytes by suppressing <i>ERO1α</i> expression via cooperation between DNMT1 and G9a

Shen, Jiangyong; Jiao, Yun; Ding, Ning; Xie, Lin; Ma, Shengchao; Zhang, Hui; Ai, Yang; Zhang, Huiping; Jiang, Yideng

doi:10.1002/cbin.11805

Cited by 7 publications

(2 citation statements)

References 34 publications

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“…However, n6-methyladenosine (m6A) modification and editing can reverse this phenomenon and increase pyroptosis in pulmonary artery endothelial cells [ 151 ]. Under the interaction of DNMT1 and HMT G9a, homocysteine inhibits the expression of reticulo-oxidoreductase 1α (ERO1α), activates the occurrence of endoplasmic reticulum stress and hepatocyte apoptosis, causing liver injury [ 152 ]. In addition, DNA methylases are also involved in the progression of chronic kidney disease to renal cell carcinoma [ 153 ].…”

Section: Types Of Chromatin Modifiersmentioning

confidence: 99%

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Nie,

Song,

Huang

et al. 2024

Mol Biomed

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The field of transcriptional regulation has revealed the vital role of chromatin modifiers in human diseases from the beginning of functional exploration to the process of participating in many types of disease regulatory mechanisms. Chromatin modifiers are a class of enzymes that can catalyze the chemical conversion of pyrimidine residues or amino acid residues, including histone modifiers, DNA methyltransferases, and chromatin remodeling complexes. Chromatin modifiers assist in the formation of transcriptional regulatory circuits between transcription factors, enhancers, and promoters by regulating chromatin accessibility and the ability of transcription factors to acquire DNA. This is achieved by recruiting associated proteins and RNA polymerases. They modify the physical contact between cis-regulatory factor elements, transcription factors, and chromatin DNA to influence transcriptional regulatory processes. Then, abnormal chromatin perturbations can impair the homeostasis of organs, tissues, and cells, leading to diseases. The review offers a comprehensive elucidation on the function and regulatory mechanism of chromatin modifiers, thereby highlighting their indispensability in the development of diseases. Furthermore, this underscores the potential of chromatin modifiers as biomarkers, which may enable early disease diagnosis. With the aid of this paper, a deeper understanding of the role of chromatin modifiers in the pathogenesis of diseases can be gained, which could help in devising effective diagnostic and therapeutic interventions.

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Section: Types Of Chromatin Modifiersmentioning

confidence: 99%

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Nie,

Song,

Huang

et al. 2024

Mol Biomed

View full text Add to dashboard Cite

show abstract

“…Using bioinformatic analysis, Liu et al and Shi et al found that the promoter methylation of ERO1α was markedly reduced in lung cancer, suggesting that hypomethylation of the promoter relieved transcription inhibition, resulting in the overexpression of ERO1α [64,67]. In a study focusing on liver cell apoptosis, DNA methyltransferase 1 (DNMT1) and G9a (also known as euchromatic histonelysine N-methyltransferase 2 (EHMT2)) were shown to be responsible for the reduction of ERO1α by mediating the hypermethylation and H3K9me2 modification of the ERO1α promoter, respectively [92].…”

Section: Regulation Of Ero1α In Tumorsmentioning

confidence: 99%

Biological mechanisms and clinical significance of endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) in human cancer

Chen,

Sharma,

Weiher

et al. 2024

J Exp Clin Cancer Res

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A firm link between endoplasmic reticulum (ER) stress and tumors has been wildly reported. Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α), an ER-resident thiol oxidoreductase, is confirmed to be highly upregulated in various cancer types and associated with a significantly worse prognosis. Of importance, under ER stress, the functional interplay of ERO1α/PDI axis plays a pivotal role to orchestrate proper protein folding and other key processes. Multiple lines of evidence propose ERO1α as an attractive potential target for cancer treatment. However, the unavailability of specific inhibitor for ERO1α, its molecular inter-relatedness with closely related paralog ERO1β and the tightly regulated processes with other members of flavoenzyme family of enzymes, raises several concerns about its clinical translation. Herein, we have provided a detailed description of ERO1α in human cancers and its vulnerability towards the aforementioned concerns. Besides, we have discussed a few key considerations that may improve our understanding about ERO1α in tumors.

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Homocysteine facilitates endoplasmic reticulum stress and apoptosis of hepatocytes by suppressing ERO1α expression via cooperation between DNMT1 and G9a

Shen

Jiao

Ding

et al. 2022

Cell Biology International

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Endoplasmic reticulum (ER) stress and apoptosis play a critical role in liver injury.Endoplasmic reticulum oxidoreductase 1α (ERO1α) is an oxidase that exists in the luminal side of the ER membrane, participating in protein folding and secretion and inhibiting apoptosis, but the underlying mechanism on liver injury induced by homocysteine (Hcy) remains obscure. In this study, hyperhomocysteinemia (HHcy) mice model was established in cbs +/− mice by feeding a high-methionine diet for 12 weeks; and cbs +/− mice fed with high-methionine diet exhibited more severe liver injury compared to cbs +/+ mice. Mechanistically, we found that Hcy promoted ER stress and apoptosis of hepatocytes and thereby aggravated liver injury through inhibiting ERO1α expression; accordingly, overexpression of ERO1α remarkably alleviated ER stress and apoptosis of hepatocytes induced by Hcy. Epigenetic modification analysis revealed that Hcy significantly increased levels of DNA methylation and H3 lysine 9 dimethylation (H3K9me2) on ERO1α promoter, which attributed to upregulated DNA methyltransferase 1 (DNMT1) and G9a, respectively.Further study showed that DNMT1 and G9a cooperatively regulated ERO1α

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Homocysteine facilitates endoplasmic reticulum stress and apoptosis of hepatocytes by suppressing ERO1α expression via cooperation between DNMT1 and G9a

Cited by 7 publications

References 34 publications

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Biological mechanisms and clinical significance of endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) in human cancer

Homocysteine facilitates endoplasmic reticulum stress and apoptosis of hepatocytes by suppressing ERO1α expression via cooperation between DNMT1 and G9a

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