Dataset Information

MiR-29b-3p Inhibitor Alleviates Hypomethylation-Related Aberrations Through a Feedback Loop Between miR-29b-3p and DNA Methylation in Cardiomyocytes.

ABSTRACT: As a member of the miR-29 family, miR-29b regulates global DNA methylation through target DNA methyltransferases (DNMTs) and acts as both a target and a key effector in DNA methylation. In this study, we found that miR-29b-3p expression was inversely correlated with DNMT expression in the heart tissues of patients with congenital heart disease (CHD), but whether it interacts with DNMTs in cardiomyocytes remains unknown. Further results revealed a feedback loop between miR-29b-3p and DNMTs in cardiomyocytes. Moreover, miR-29b-3p inhibitor relieved the deformity of hypomethylated zebrafish and restored the DNA methylation patterns in cardiomyocytes, resulting in increased proliferation and renormalization of gene expression. These results suggest mutual regulation between miR-29b-3p and DNMTs in cardiomyocytes and support the epigenetic normalization of miRNA-based therapy in cardiomyocytes.

SUBMITTER: Wu F

PROVIDER: S-EPMC9035530 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

miR-29b-3p Inhibitor Alleviates Hypomethylation-Related Aberrations Through a Feedback Loop Between miR-29b-3p and DNA Methylation in Cardiomyocytes.

Wu Fang F Yang Qian Q Mi Yaping Y Wang Feng F Cai Ke K Zhang Yawen Y Wang Youhua Y Wang Xu X Gui Yonghao Y Li Qiang Q

Frontiers in cell and developmental biology 20220411

As a member of the miR-29 family, miR-29b regulates global DNA methylation through target DNA methyltransferases (DNMTs) and acts as both a target and a key effector in DNA methylation. In this study, we found that miR-29b-3p expression was inversely correlated with DNMT expression in the heart tissues of patients with congenital heart disease (CHD), but whether it interacts with DNMTs in cardiomyocytes remains unknown. Further results revealed a feedback loop between miR-29b-3p and DNMTs in car ...[more]

PMID: 35478963

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Project description:BackgroundOur previous research suggested that dexmedetomidine (Dex) promotes autophagy in cardiomyocytes, thus safeguarding them against apoptosis during sepsis. However, the underlying mechanisms of Dex-regulated autophagy have remained elusive. This study aimed to explore the role of exosomes and how they participate in Dex-induced cardioprotection in sepsis. The underlying microRNA (miRNA) mechanisms and possible therapeutic targets for septic myocardial injury were identified.MethodsWe first collected plasma exosomes from rats with sepsis induced by caecal ligation and puncture (CLP) with or without Dex treatment, and then incubated them with H9c2 cells to observe the effect on cardiomyocytes. Subsequently, the differential expression of miRNAs in plasma exosomes from each group of rats was identified through miRNA sequencing. miR-29b-3p expression in circulating exosomes of septic or non-septic patients, as well as in lipopolysaccharide-induced macrophages after Dex treatment, was analysed by quantitative real-time polymerase chain reaction (qRT-PCR). The autophagy level of cardiomyocytes after macrophage-derived exosome treatment was assessed by an exosome tracing assay, western blotting, and an autophagic flux assay. Specific miRNA mimics and inhibitors or small interfering RNAs were used to predict and evaluate the function of candidate miRNA and its target genes by qRT-PCR, annexin V/propyl iodide staining, autophagy flux analysis, and western blotting.ResultsWe found that plasma-derived exosomes from Dex-treated rats promoted cardiomyocyte autophagy and exerted antiapoptotic effects. Additionally, they exhibited a high expression of miRNA, including miR-29b-3p. Conversely, a significant decrease in miR-29b-3p was observed in circulating exosomes from CLP rats, as well as in plasma exosomes from sepsis patients. Furthermore, Dex upregulated the lipopolysaccharide-induced decrease in miR-29b-3p expression in macrophage-derived exosomes. Exosomal miR-29b-3p from macrophages is thought to be transferred to cardiomyocytes, thus leading to the promotion of autophagy in cardiomyocytes. Database predictions, luciferase reporter assays, and small interfering RNA intervention confirmed that glycogen synthase kinase 3β (GSK-3β) is a target of miR-29b-3p. miR-29b-3p promotes cardiomyocyte autophagy by inhibiting GSK-3β expression and activation.ConclusionsThese findings demonstrate that Dex attenuates sepsis-associated myocardial injury by modulating exosome-mediated macrophage-cardiomyocyte crosstalk and that the miR-29b-3p/GSK-3β signaling pathway represents a hopeful target for the treatment of septic myocardial injury.

Dataset Information

MiR-29b-3p Inhibitor Alleviates Hypomethylation-Related Aberrations Through a Feedback Loop Between miR-29b-3p and DNA Methylation in Cardiomyocytes.

Publications

miR-29b-3p Inhibitor Alleviates Hypomethylation-Related Aberrations Through a Feedback Loop Between miR-29b-3p and DNA Methylation in Cardiomyocytes.

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