Emerging Role of Epitranscriptomics in Diabetes Mellitus and Its Complications

Geng, Xue; Li, Zheng; Yang, Ying

doi:10.3389/fendo.2022.907060

Cited by 12 publications

(5 citation statements)

References 248 publications

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“…Epigenetic research is currently one of the most relevant hot topics due to the reversible characteristics of its mechanisms, plasticity and phenotype impact, which provide new therapeutic targets for retinal diseases. 11 – 13 However, despite the fact that some studies focused on gene transcription associated with cellular behavior in response to environmental changes, in animal or in vitro studies, 18 , 25 using non-uniform methodological approaches, 26 , 27 which addressed primarily the risk of developing DM or DR, epigenetic studies of DME are still scarce. In fact, epigenetic involvement has been previously studied in relevant mechanisms related to DM and DR (inflammation, oxidative stress, apoptosis) that may be important for therapeutic resistance and retinal impairment due to “metabolic memory”.…”

Section: Discussionmentioning

confidence: 99%

DNA methyltransferase expression (DNMT1, DNMT3a and DNMT3b) as a potential biomarker for anti-VEGF diabetic macular edema response

Camacho

Ribeiro

Pereira

et al. 2023

European Journal of Ophthalmology

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Purpose DNA methylation is involved in Diabetic Retinopathy progression showing a metabolic memory mechanism. However, the association of DNA methyltransferase with diabetic macular edema is still unknown. We aimed to describe the differences in DNA methyltransferase gene expression in patients with different diabetic macular edema responses. Methods A total of 27 diabetic patients, aged 59–90 years, were prospectively enrolled in this cross-sectional study. The participants were classified into control group (CG, n = 11), diabetic macular edema responders (rDME, n = 9) and non-responder diabetic macular edema (nrDME, n = 7) after anti-vascular endothelial growth factor (anti-VEGF) treatment. Only cases with a complete ophthalmological examination, digital 133° color fundus, and SD-OCT assessments were used. After RNA extraction and first-strand cDNA synthesis, quantitative real-time PCR was performed with specific primers on the CFX Connect™ Real-Time PCR Detection System to assess differential transcriptional expression patterns. Results The DNMT1 gene showed a positive correlation (r = 0.617; p = 0.043) with Best Corrected Visual Acuity (BCVA) in CG, a positive correlation (r = 0.917; p = 0.010) with HbA1c in nrDME and a negative correlation (r = −0.659; p = 0.049) with GCL-IPL thickness in rDME. DNMT3A gene showed a positive correlation (r = −0.890; p = 0.001) with Sub-foveal Choroidal thickness in rDME whereas DNMT3b gene showed a negative correlation (r = −0.815; p = 0.007) with HbA1c and RNFL (r = −0.664; p = 0.026) in CG. Conclusions Patients with similar metabolic profile risk factors showed associated DNA methyltransferase transcriptional expression patterns differences fitting with the anti-VEGF diabetic macular edema response. Further studies are needed to clarify if these results (1) reflect disease evolution, (2) translate the therapeutic impact, (3) or can help to predict the therapeutic resistance profile.

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Section: Discussionmentioning

confidence: 99%

DNA methyltransferase expression (DNMT1, DNMT3a and DNMT3b) as a potential biomarker for anti-VEGF diabetic macular edema response

Camacho

Ribeiro

Pereira

et al. 2023

European Journal of Ophthalmology

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“…(5) Epitranscriptomic modifications, including the N 6 -methyladenosine (m 6 A), have been shown to regulate the processing, translation, and stability of mRNAs; thereby influencing cell biology ( 16 ). Posttranscriptional epigenetic modification of RNA (the so-called ‘epitranscriptome’) has emerged as a fascinating field of research (for a detailed discussion on this topic, readers can refer to several excellent reviews ( 17 – 19 ).…”

Section: Interplay Between Cellular Metabolism and Epigenomementioning

confidence: 99%

Metabolo-epigenetic interplay provides targeted nutritional interventions in chronic diseases and ageing

Gómez de Cedrón,

Moreno Palomares,

Ramírez de Molina

2023

Front. Oncol.

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Epigenetic modifications are chemical modifications that affect gene expression without altering DNA sequences. In particular, epigenetic chemical modifications can occur on histone proteins -mainly acetylation, methylation-, and on DNA and RNA molecules -mainly methylation-. Additional mechanisms, such as RNA-mediated regulation of gene expression and determinants of the genomic architecture can also affect gene expression. Importantly, depending on the cellular context and environment, epigenetic processes can drive developmental programs as well as functional plasticity. However, misbalanced epigenetic regulation can result in disease, particularly in the context of metabolic diseases, cancer, and ageing. Non-communicable chronic diseases (NCCD) and ageing share common features including altered metabolism, systemic meta-inflammation, dysfunctional immune system responses, and oxidative stress, among others. In this scenario, unbalanced diets, such as high sugar and high saturated fatty acids consumption, together with sedentary habits, are risk factors implicated in the development of NCCD and premature ageing. The nutritional and metabolic status of individuals interact with epigenetics at different levels. Thus, it is crucial to understand how we can modulate epigenetic marks through both lifestyle habits and targeted clinical interventions -including fasting mimicking diets, nutraceuticals, and bioactive compounds- which will contribute to restore the metabolic homeostasis in NCCD. Here, we first describe key metabolites from cellular metabolic pathways used as substrates to “write” the epigenetic marks; and cofactors that modulate the activity of the epigenetic enzymes; then, we briefly show how metabolic and epigenetic imbalances may result in disease; and, finally, we show several examples of nutritional interventions - diet based interventions, bioactive compounds, and nutraceuticals- and exercise to counteract epigenetic alterations.

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“…To date, more than 160 chemical modifications have been discovered in RNA. These modifications can affect the function and metabolic process of RNA and are considered important regulators of gene expression [ 7 ]. Therefore, RNA methylation has become an important and rapidly developing research topic in biomedical research [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

NSUN2 affects diabetic retinopathy progression by regulating MUC1 expression through RNA m5C methylation

Wang,

Xue,

Kan

et al. 2024

J Transl Med

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Background Diabetic retinopathy (DR) is the leading cause of blinding eye disease among working adults and is primarily attributed to the excessive proliferation of microvessels, which leads to vitreous hemorrhage and retinal traction, thereby significantly impairing patient vision. NSUN2-mediated RNA m5C methylation is implicated in various diseases, and in this investigation, we focused on elucidating the impact of NSUN2 on the regulation of the expression of the downstream gene MUC1, specifically through RNA m5C methylation, on the progression of DR. Method Utilizing Microarray analysis, we examined patient vitreous fluid to pinpoint potential therapeutic targets for DR. Differential expression of NSUN2 was validated through qRT-PCR, Western blot, and immunofluorescence in human tissue, animal tissue, and cell model of DR. The relationship between NSUN2 and DR was explored in vitro and in vivo through gene knockdown and overexpression. Various techniques, such as MeRIP-qPCR and dot blot, were applied to reveal the downstream targets and mechanism of action of NSUN2. Results The levels of both NSUN2 and RNA m5C methylation were significantly elevated in the DR model. Knockdown of NSUN2 mitigated DR lesion formation both in vitro and in vivo. Mechanistically, NSUN2 promoted MUC1 expression by binding to the RNA m5C reader ALYREF. Knockdown of ALYREF resulted in DR lesion alterations similar to those observed with NSUN2 knockdown. Moreover, MUC1 overexpression successfully reversed a series of DR alterations induced by NSUN2 silencing. Conclusions NSUN2 regulates the expression of MUC1 through ALYREF-mediated RNA m5C methylation, thereby regulating the progression of DR and providing a new option for the treatment of DR in the future.

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Emerging Role of Epitranscriptomics in Diabetes Mellitus and Its Complications

Cited by 12 publications

References 248 publications

DNA methyltransferase expression (DNMT1, DNMT3a and DNMT3b) as a potential biomarker for anti-VEGF diabetic macular edema response

DNA methyltransferase expression (DNMT1, DNMT3a and DNMT3b) as a potential biomarker for anti-VEGF diabetic macular edema response

Metabolo-epigenetic interplay provides targeted nutritional interventions in chronic diseases and ageing

NSUN2 affects diabetic retinopathy progression by regulating MUC1 expression through RNA m5C methylation

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