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

Lv, Xiaobing; Niu, Qinghui; Zhang, Min; Li, Feng; Feng, Jia

doi:10.1002/kjm2.12309

Cited by 6 publications

(4 citation statements)

References 26 publications

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“…in this study, it was found that Hdac2-mediated H3K14 hyperacetylation contributed to mir-30a-5p upregulation in HPostc. in recent years, accumulating evidence has demonstrated that mir-30a-5p participates in cardiovascular pathophysiology (39)(40)(41). although several studies have indicated the importance of mir-30a-5p in cardiovascular diseases, there are still conflicting views.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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-5p has been reported to be highly expressed in the damaged heart [ 33 ] and patients with HF, left ventricular dysfunction, and left ventricular hypertrophy [ 8 , 20 , 34 ]. Silencing of miR-30a-5p promoted recovery of cardiac injury, and protected cardiomyocytes from the impact of hypoxia/reoxygenation [ 35 ]. Studies of miR-654-5p in regulating cancer has been reported [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic potential of a circulating miRNA model associated with therapeutic effect in heart failure

Zhao

et al. 2022

J Transl Med

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Heart failure (HF), as the leading cause of death, is continuing to increase along with the aging of the general population all over the world. Identification of diagnostic biomarkers for early detection of HF is considered as the most effective way to reduce the risk and mortality. Herein, we collected plasma samples from HF patients (n = 40) before and after medical therapy to determine the change of circulating miRNAs through a quantitative real-time PCR (QRT-PCR)-based miRNA screening analysis. miR-30a-5p and miR-654-5p were identified as the most significantly changed miRNAs in the plasma of patients upon treatment. In consistence, miR-30a-5p showed upregulation and miR-654-5p showed downregulation in the circulation of 30 HF patients, compared to 15 normal controls in the training phase, from which a two-circulating miRNA model was developed for HF diagnosis. Next, we performed the model validation using an independent cohort including 50 HF patients and 30 controls. As high as 98.75% of sensitivity and 95.00% of specificity were achieved. A comparison between the miRNA model and NT-pro BNP in diagnostic accuracy of HF indicated an upward trend of the miRNA model. Moreover, change of the two miRNAs was further verified in association with the therapeutic effect of HF patients, in which miR-30a-5p showed decrease while miR-654-5p showed increase in the plasma of patients after LVAD implantation. In conclusion, the current study not only identified circulating miR-654-5p for the first time as a novel biomarker of HF, but also developed a novel 2-circulating miRNA model with promising potentials for diagnosis and prognosis of HF patients, and in association with therapeutic effects as well.

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“…Among the 11 miRNAs predicted (miR-2682-5p, miR-34b-5p, miR-449 c-5p, miR-545-5p, miR-30b-5p, miR-30a-5p, miR-30e-5p, miR-30 c-5p, miR-30d-5p, miR-770-5p, and miR-4712-5p), miR-30a-5p expression was remarkably higher in HTR-8/ SVneo cells transfected with si-circPUM1 (Figure 2a). It has been demonstrated by previous reports that miR-30a-5p represses cell viability, migration, and invasion, accelerates cell apoptosis, and exacerbates inflammatory response [25][26][27]. Therefore, miR-30a-5p was selected as the target miRNA for circPUM1 in this work.…”

Section: Circpum1 Sponges Mir-30a-5p In Htr-8/svneo Cellsmentioning

confidence: 97%

Circular RNA PUM1 (CircPUM1) attenuates trophoblast cell dysfunction and inflammation in recurrent spontaneous abortion via the MicroRNA-30a-5p (miR-30a-5p)/JUNB axis

Zhu

Shi

et al. 2021

Bioengineered

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Recurrent spontaneous abortion (RSA) is a threat to human reproductive health worldwide. CircPUM1 has been reported to participate in the pathogenesis of various diseases. However, there has been no report on its association with RSA yet. In this study, gene expressions were examined by RT-qPCR. Protein levels of JUNB and cleaved caspases-3 were detected by Western blotting. ELISA was used to detect TNF-α, IL-6, and IL-8 levels. Cell viability, migration, invasion, and apoapsis were analyzed using CCK-8, transwell, and flow cytometry assays. The association between miR-30a-5p and circPUM1 or JUNB was identified by bioinformatics analysis, dualluciferase reporter assay, and RIP assay. Herein, we found circPUM1 was significantly downregulated in RSA placental samples. CircPUM1 knockdown induced decreased proliferation, migration, and invasion, but increased apoptosis, pro-apoptotic protein (cleaved caspases-3) level, and proinflammatory factor (TNF-α, IL-6, and IL-8) secretion in trophoblast cells. Furthermore, we confirmed that circPUM1 was a sponge for miR-30a-5p, and JUNB was directly targeted by miR-30a-5p. It was demonstrated that miR-30a-5p inhibition could reverse trophoblast cell dysfunction and inflammation induced by circPUM1 knockdown. In addition, we found that JUNB expression was negatively modulated by miR-30a-5p and positively regulated by circPUM1. Moreover, circPUM1 inhibition exacerbated dysfunction and inflammation in trophoblast cells via targeting JUNB. To sum up, our study indicated that circPUM1 could impair RSA occurrence and development by facilitating trophoblast cellular processes and protecting against inflammation via the miR-30a-5p/JUNB axis, providing a new target for the improvement of RSA diagnosis and treatment.

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

Cited by 6 publications

References 26 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

Diagnostic potential of a circulating miRNA model associated with therapeutic effect in heart failure

Circular RNA PUM1 (CircPUM1) attenuates trophoblast cell dysfunction and inflammation in recurrent spontaneous abortion via the MicroRNA-30a-5p (miR-30a-5p)/JUNB axis

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