DNA methyltransferase 1 (DNMT1) suppresses mitophagy and aggravates heart failure via the microRNA-152-3p/ETS1/RhoH axis

Deng, Zhuo-Jun; Yao, Jiaqi; Xiao, Na; Yu, Han; Wu, Xuan; Ci, Caizhe; Chen, Ke; Geng, Xilin

doi:10.1038/s41374-022-00740-8

Cited by 20 publications

(14 citation statements)

References 42 publications

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“…Functional ncRNA plays a role in regulatory mechanisms of HF, leading to ventricular remodeling, hypertrophy, and myocardial apoptosis. A recent study indicated that the suppression of miRNA-152-3p improved the expression of ETS1 , promoting the development of HF [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Expression Profile of Inflammation Response Genes and Potential Regulatory Mechanisms in Dilated Cardiomyopathy

Liang

Sun

Teng

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. The inflammatory response is important in dilated cardiomyopathy (DCM). However, the expression of inflammatory response genes (IRGs) and regulatory mechanisms in DCM has not been well characterized. Methods. We analyzed 27,665 cells of single-cell RNA sequencing dataset of four DCM samples and two healthy controls (HC). IRGs among differentially expressed genes (DEGs) of active cell clusters were screened from the Molecular Signatures Database (MSigDB). The bulk sequencing dataset of 166 DCM patients and 166 HC was analyzed to explore the common IRGs. The biological functions of the IRGs were analyzed according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. IRG-related transcription factors (TFs) were determined using the TRRUST database. The protein–protein interaction (PPI) network was constructed using the STRING database. Then, we established the noncoding RNA (ncRNA) regulatory network based on the StarBase database. Finally, the potential drugs that target IRGs were explored using the Drug Gene Interaction Database (DGIdb). Results. The proportions of dendritic cells (DCs), B cells, NK cells, and T cells were increased in DCM patients, whereas monocytes were decreased. DCs expressed more IRGs in DCM. The GO and KEGG analyses indicated that the functional characteristics of active cells mainly focused on the immune response. Thirty-nine IRGs were commonly expressed among active cell cluster DEGs, bulk RNA DEGs, and inflammatory response-related genes. ETS1 plays an important role in regulation of IRG expression. The competing endogenous RNA regulatory network showed the relationship between ncRNA and IRGs. Sankey diagram showed that arachidonate 5-lipoxygenase (ALOX5) played a major role in regulation between TFs and potential drugs. Conclusion. DCs infiltrate into the myocardium and contribute to the immune response in DCM. The transcription factor ETS1 plays an important role in regulation of IRGs. Moreover, ALOX5 may be a potential therapeutic target for DCM.

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Section: Discussionmentioning

confidence: 99%

Expression Profile of Inflammation Response Genes and Potential Regulatory Mechanisms in Dilated Cardiomyopathy

Liang

Sun

Teng

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Methylation-specific PCR (MSP) results showed that DNMT1 inhibited the expression of miR-152-3p by increasing DNA methylation in the miR-152-3p promoter region. Transfection of miR-152-3p mimics significantly reduced the luciferase activity of E26 transformation specific-1 (ETS1)-3’UTR-wt, while ETS1 regulates Ras homolog gene family member H (RhoH) in myoblasts, and DNMT1 may inhibit miR-152-3p expression by promoting methylation inhibition of miR-152-3p and enhancing the expression of ETS1, thereby inducing RHOH transcription activation and inhibiting mitochondrial autophagy, ultimately promoting the development of heart failure [ 199 ].…”

Section: Mirna As a Therapeutic Target Of Dicmentioning

confidence: 99%

MicroRNA in the Diagnosis and Treatment of Doxorubicin-Induced Cardiotoxicity

Kuang

Tan

et al. 2023

Biomolecules

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Doxorubicin (DOX), a broad-spectrum chemotherapy drug, is widely applied to the treatment of cancer; however, DOX-induced cardiotoxicity (DIC) limits its clinical therapeutic utility. However, it is difficult to monitor and detect DIC at an early stage using conventional detection methods. Thus, sensitive, accurate, and specific methods of diagnosis and treatment are important in clinical practice. MicroRNAs (miRNAs) belong to non-coding RNAs (ncRNAs) and are stable and easy to detect. Moreover, miRNAs are expected to become biomarkers and therapeutic targets for DIC; thus, there are currently many studies focusing on the role of miRNAs in DIC. In this review, we list the prominent studies on the diagnosis and treatment of miRNAs in DIC, explore the feasibility and difficulties of using miRNAs as diagnostic biomarkers and therapeutic targets, and provide recommendations for future research.

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“…miR-147-y achieves its effect by targeting Raptor, a subunit of mTOR complex 1 (mTORC1) and a potential negative regulator of mitophagy ( Gao et al, 2022 ). Another recent article found that DOX suppresses mitophagy by reducing miR-152-3p expression via DNA methyltransferase 1 (DNMT1) ( Deng et al, 2022 ). When DNMT1 is inactive, miR-153-3p enhances mitophagy by targeting E26 transformation specific-1 (ETS1) ( Deng et al, 2022 ).…”

Section: Mirnas Involved In Dox-induced Mitochondrial Fission and Mit...mentioning

confidence: 99%

“…Another recent article found that DOX suppresses mitophagy by reducing miR-152-3p expression via DNA methyltransferase 1 (DNMT1) ( Deng et al, 2022 ). When DNMT1 is inactive, miR-153-3p enhances mitophagy by targeting E26 transformation specific-1 (ETS1) ( Deng et al, 2022 ). Both studies seem to support the idea that DOX suppresses cardiac mitophagy.…”

Section: Mirnas Involved In Dox-induced Mitochondrial Fission and Mit...mentioning

confidence: 99%

MicroRNAs in doxorubicin-induced cardiotoxicity: The DNA damage response

Kawano

Adamcová

2022

Front. Pharmacol.

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Doxorubicin (DOX) is a chemotherapeutic drug widely used for cancer treatment, but its use is limited by cardiotoxicity. Although free radicals from redox cycling and free cellular iron have been predominant as the suggested primary pathogenic mechanism, novel evidence has pointed to topoisomerase II inhibition and resultant genotoxic stress as the more fundamental mechanism. Recently, a growing list of microRNAs (miRNAs) has been implicated in DOX-induced cardiotoxicity (DIC). This review summarizes miRNAs reported in the recent literature in the context of DIC. A particular focus is given to miRNAs that regulate cellular responses downstream to DOX-induced DNA damage, especially p53 activation, pro-survival signaling pathway inhibition (e.g., AMPK, AKT, GATA-4, and sirtuin pathways), mitochondrial dysfunction, and ferroptosis. Since these pathways are potential targets for cardioprotection against DOX, an understanding of how miRNAs participate is necessary for developing future therapies.

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DNA methyltransferase 1 (DNMT1) suppresses mitophagy and aggravates heart failure via the microRNA-152-3p/ETS1/RhoH axis

Cited by 20 publications

References 42 publications

Expression Profile of Inflammation Response Genes and Potential Regulatory Mechanisms in Dilated Cardiomyopathy

Expression Profile of Inflammation Response Genes and Potential Regulatory Mechanisms in Dilated Cardiomyopathy

MicroRNA in the Diagnosis and Treatment of Doxorubicin-Induced Cardiotoxicity

MicroRNAs in doxorubicin-induced cardiotoxicity: The DNA damage response

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