DNA Hypomethylation of miR-30a Mediated the Protection of Hypoxia Postconditioning Against Aged Cardiomyocytes Hypoxia/Reoxygenation Injury Through Inhibiting Autophagy

Wang, Yanhua; Hao, Yinju; Zhang, Hui; Xu, Lingbo; Ding, Ning; Wang, Rui; Zhu, Gangjie; Ma, Shengchao; Ai, Yang; Yang, Yong; Wu, Kai; Jiang, Yibin; Zhang, Huiping; Jiang, Yideng

doi:10.1253/circj.cj-19-0915

Cited by 19 publications

(21 citation statements)

References 45 publications

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“…H9c2 rat cardiomyocytes (The cell Bank of Type culture collection of The chinese academy of Sciences) were cultured in dMeM (Gibco; Thermo Fisher Scientific, Inc.) supplemented with 10% fetal bovine serum (Gibco; Thermo Fisher Scientific, inc.) and 1% penicillin streptomycin in 5% co 2 at 37˚C in a humified atmosphere. Senescent cardiomyocytes were established by 8 mg/ml d-galactose (Shanghai Bio-Tech co., ltd.) treatment of H9C2 cells for 9 days, which was based on findings from our previous study where increased senescence-associated β-galactosidase (Sa-β-gal)-positive cells were identified using a Senescence β-Galactosidase staining kit (Beijing Solarbio Science & Technology co., ltd.) (8). Furthermore, H/r and HPostc models were established as previously reported (8).…”

Section: Methodsmentioning

confidence: 99%

“…Senescent cardiomyocytes were established by 8 mg/ml d-galactose (Shanghai Bio-Tech co., ltd.) treatment of H9C2 cells for 9 days, which was based on findings from our previous study where increased senescence-associated β-galactosidase (Sa-β-gal)-positive cells were identified using a Senescence β-Galactosidase staining kit (Beijing Solarbio Science & Technology co., ltd.) (8). Furthermore, H/r and HPostc models were established as previously reported (8). Senescent cardiomyocytes were treated with 200 nmol/l Trichostatin a (TSa; cat.…”

Section: Methodsmentioning

confidence: 99%

“…mir-30a-5p, a member of the mir-30 family, is regarded as a key mirna in cardiovascular pathophysiology (7). in addition, our previous study demonstrated that hypoxia postconditioning (HPostc) protected aged cardiomyocytes from hypoxia/reoxygenation (H/r) injury via dna methyltransferase 3B (dnMT3B)-regulated mir-30a-5p, suggesting that mir-30a-5p may be a potential novel target for ischemic Mi (8). However, the underlying mechanism involved in iPostc protection against aging myocardial i/r injury has not yet been elucidated.…”

Section: Introductionmentioning

confidence: 99%

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H3K14 hyperacetylation‑mediated c‑Myc binding to the miR‑30a‑5p gene promoter under hypoxia postconditioning protects senescent cardiomyocytes from hypoxia/reoxygenation injury

Zhang

Wang

et al. 2021

Mol Med Rep

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our previous study reported that microrna (mir)-30a-5p upregulation under hypoxia postconditioning (HPostc) exert a protective effect on aged H9c2 cells against hypoxia/reoxygenation injury via dna methyltransferase 3B-induced dna hypomethylation at the mir-30a-5p gene promoter. This suggests that mir-30a-5p may be a potential preventative and therapeutic target for ischemic heart disease in aged myocardium. The present study aimed to investigate the underlying mechanisms of mir-30a-5p transcription in aged myocardium in ischemic heart disease. cardiomyocytes were treated with 8 mg/ml d-galactose for 9 days, and then exposed to hypoxic conditions. cell viability was determined using a cell viability assay. expression levels of histone deacetylase 2 (Hdac2), lc3B-ii/i, beclin-1 and p62 were detected via reverse transcription-quantitative Pcr and western blotting. chromatin immunoprecipitation-Pcr and luciferase reporter assays were performed to evaluate the effect of c-Myc binding and activity on the mir-30a-5p promoter in senescent cardiomyocytes following HPostc. it was found that HPostc enhanced the acetylation levels of H3K14 at the mir-30a-5p gene promoter in senescent cardiomyocytes, which attributed to the decreased expression of Hdac2. in addition, c-Myc could positively regulate mir-30a-5p transcription to inhibit senescent cardiomyocyte autophagy. Mechanically, it was observed that increased H3K14 acetylation level exposed to romidepsin facilitated c-Myc binding to the mir-30a-5p gene promoter region, which led to the increased transcription of mir-30a-5p. Taken together, these results demonstrated that Hdac2-mediated H3K14 hyperacetylation promoted c-Myc binding to the mir-30a-5p gene promoter, which contributed to HPostc senescent cardioprotection.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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H3K14 hyperacetylation‑mediated c‑Myc binding to the miR‑30a‑5p gene promoter under hypoxia postconditioning protects senescent cardiomyocytes from hypoxia/reoxygenation injury

Zhang

Wang

et al. 2021

Mol Med Rep

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“…miR-30a has been demonstrated to increase autophagy in hypoxia-exposed cardiomyocytes [ 31 ], while downregulation of miR-30e could inhibit apoptosis to protect the heart from myocardial ischemia/reperfusion injury [ 32 ]. Interestingly, studies have also demonstrated that overexpression of miR-30a inhibits autophagy to alleviate hypoxia/reoxygenation injury in cardiomyocytes [ 33 ]. Upregulation of miR-30e-5p has been shown to alleviate hypoxia-induced apoptosis by targeting Bim to protect cardiomyocytes [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

miR-30e-3p Promotes Cardiomyocyte Autophagy and Inhibits Apoptosis via Regulating Egr-1 during Ischemia/Hypoxia

Wang

Sun

et al. 2020

BioMed Research International

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Background. Microvascular obstruction (MVO) can result in coronary microcirculation embolism and myocardial microinfarction. Myocardial injury induced by MVO is characterized by continuous ischemia and hypoxia of cardiomyocytes. Autophagy and apoptosis are closely associated with various cardiovascular diseases. Based on our previous study, we observed a decrease in miR-30e-3p expression and an increase in Egr-1 expression in a rat coronary microembolization model. However, the specific function of miR-30e-3p in regulating autophagy and apoptosis in an ischemia/hypoxia (IH) environment remains to be deciphered. We exposed cardiomyocytes to an IH environment and then determined whether miR-30e-3p was involved in promoting cardiomyocyte autophagy and inhibiting apoptosis by regulating Egr-1. Methods. Cardiomyocytes were isolated from rats for our in vitro study. miR-30e-3p was either overexpressed or inhibited by transfection with lentiviral vectors into cardiomyocytes. 3-Methyladenine (3-MA) was used to inhibit autophagy. RT-qPCR and western blotting were used to determine the expression levels of miR-30e-3p, Egr-1, and proteins related to the autophagy and apoptosis process. Autophagic vacuoles and autophagic flux were evaluated using transmission electron microscopy (TEM) and confocal microscopy, respectively. Cardiomyocyte viability was evaluated using the MTS assay. Cell injury was assessed by lactate dehydrogenase (LDH) leakage, and apoptosis was determined by flow cytometry. Results. Both miR-30e-3p expression and autophagy were significantly inhibited, and apoptosis was increased in cardiomyocytes after 9 hours of IH exposure. Overexpression of miR-30e-3p increased autophagy and inhibited apoptosis, as well as suppressed Egr-1 expression and decreased cell injury. In addition, inhibition of miR-30e-3p reduced autophagy and increased apoptosis and cell injury. Conclusions. miR-30e-3p may be involved in promoting cardiomyocyte autophagy and inhibiting apoptosis by indirectly regulating Egr-1 expression in an IH environment.

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“…MiR‐30a attenuates cardiac fibrosis in rats with myocardial infarction by inhibiting connective‐tissue growth factor (CTGF) 20 . DNA Hypomethylation of miR‐30a mediated the protection of hypoxia postconditioning against aged cardiomyocytes I/R injury through inhibiting autophagy 21 . miRNA‐30 inhibition protects against cardiac ischemic injury through modulating the expression of Cystathionine‐γ‐Lyase 22 .…”

Section: Discussionmentioning

confidence: 99%

Critical functions of microRNA‐30a‐5p‐E2F3 in cardiomyocyte apoptosis induced by hypoxia/reoxygenation

Niu

Zhang

et al. 2020

The Kaohsiung J of Med Scie

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The high‐mortality rate of cardiovascular diseases (CVDs) is associated with the myocardial ischemia and reperfusion (I/R). Recent investigations have revealed that microRNAs (miRNAs) exert vital functions in the apoptosis of cardiomyocyte cell. Nevertheless, the potential role of miR‐30a‐5p in the regulation of cardiomyocyte cell apoptosis needs to be illuminated. In the current study, we observed that hypoxia/reoxygenation (H/R) remarkably raised the level of miR‐30a‐5p but reduced the expression of E2F transcription factor 3 (E2F3) in H9c2 cardiomyocytes. In vivo, miR‐30a‐5p was found to be significantly upregulated in the hearts of rats following I/R. Downregulation of miR‐30a‐5p using anti‐miR‐30a‐5p decreased H9c2 cardiomyocytes apoptosis caused by H/R and promoted the proliferation of H9c2 inhibited by H/R. Moreover, E2F3 was a possible target gene of miR‐30a‐5p and upregulation of miR‐30a‐5p reduced the expression level of E2F3 in H9c2 cardiomyocytes. We further identified that E2F3 silencing reversed the effect of anti‐miR‐30a‐5p on the proliferation and apoptosis in H/R treated H9c2 cells. These studies suggested that downregulation of miR‐30a‐5p attenuated the impact of H/R on H9c2 cardiomyocytes through targeting E2F3.

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DNA Hypomethylation of miR-30a Mediated the Protection of Hypoxia Postconditioning Against Aged Cardiomyocytes Hypoxia/Reoxygenation Injury Through Inhibiting Autophagy

Cited by 19 publications

References 45 publications

H3K14 hyperacetylation‑mediated c‑Myc binding to the miR‑30a‑5p gene promoter under hypoxia postconditioning protects senescent cardiomyocytes from hypoxia/reoxygenation injury

H3K14 hyperacetylation‑mediated c‑Myc binding to the miR‑30a‑5p gene promoter under hypoxia postconditioning protects senescent cardiomyocytes from hypoxia/reoxygenation injury

miR-30e-3p Promotes Cardiomyocyte Autophagy and Inhibits Apoptosis via Regulating Egr-1 during Ischemia/Hypoxia

Critical functions of microRNA‐30a‐5p‐E2F3 in cardiomyocyte apoptosis induced by hypoxia/reoxygenation

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