lncRNA-ZFAS1 induces mitochondria-mediated apoptosis by causing cytosolic Ca2+ overload in myocardial infarction mice model

Jiao, Lei; Li, Mengmeng; Shao, Yingchun; Zhang, Yuanyuan; Gong, Manyu; Yang, Xuewen; Wang, Yanying; Tan, Zhongyue; Sun, Lihua; Xuan, Lina; Qi, Yu; Li, Yanru; Gao, Yuqiu; Liu, Heng; Xu, Hui; Li, Xiaohan; Zhang, Yong; Zhang, Ying

doi:10.1038/s41419-019-2136-6

Cited by 78 publications

(55 citation statements)

References 26 publications

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“…Neonatal cardiomyocytes were separated from the hearts of 1- to 3-day-old mice as previously described 23 . Briefly, neonatal mice ventricles tissues were dissected and minced into 1–2 mm 3 pieces after the hearts had been rapidly placed on ice, and neonatal cardiomyocytes were isolated in 0.25% trypsin at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

GDF11 inhibits cardiomyocyte pyroptosis and exerts cardioprotection in acute myocardial infarction mice by upregulation of transcription factor HOXA3

Li¹,

Xu²,

Liu³

et al. 2020

Cell Death Dis

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NLRP3 (Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3) inflammasome-mediated cardiomyocytes pyroptosis plays a crucial part in progression of acute myocardial infarction (MI). GDF11 (Growth Differentiation Factor 11) has been reported to generate cytoprotective effects in phylogenesis and multiple diseases, but the mechanism that GDF11 contributes to cardioprotection of MI and cardiomyocytes pyroptosis remains poorly understood. In our study, we first determined that GDF11 was abnormally downregulated in the heart tissue of MI mice and hypoxic cardiomyocytes. Moreover, AAV9-GDF11 markedly alleviated heart function in MI mice. Meanwhile, GDF11 overexpression also decreased the pyroptosis of hypoxic cardiomyocytes. PROMO and JASPAR prediction software found that transcription factor HOXA3 was predicted as an important regulator of NLRP3, and was confirmed by ChIP assay. Further analysis identifying GDF11 promoted the Smad2/3 pathway resulted in HOXA3 overexpression. Taken together, our study implies that GDF11 prevents cardiomyocytes pyroptosis via HOXA3/NLRP3 signaling pathway in MI mice.

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Section: Methodsmentioning

confidence: 99%

GDF11 inhibits cardiomyocyte pyroptosis and exerts cardioprotection in acute myocardial infarction mice by upregulation of transcription factor HOXA3

Li¹,

Xu²,

Liu³

et al. 2020

Cell Death Dis

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“…ZFAS1 is one of cardiac-related lncRNAs, previously, knockdown of lncRNA-ZFAS1 prevents cardiomyocytes from MI [14]. Reports emphasized that ZFAS1 was upregulated to promote cardiac disease [40] and induce mitochondria-mediated cardiomyocytes apoptosis [16].…”

Section: Discussionmentioning

confidence: 99%

“…Cardiac-related lncRNA-ZFAS1 (zinc nger antisense 1) was proved to associate with acute myocardial infarction [14][15][16][17]. Nevertheless, the mechanism between lncRNA-ZFAS1 with diabetic cardiomyopathy is still lacking.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the Long non-coding RNA ZFAS1 attenuates pathogenic ferroptosis by sponging miR-150-5p to activate CCND2 against diabetic cardiomyopathy

Ni¹,

Chen²,

Huang³

et al. 2021

Preprint

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Background Diabetic cardiomyopathy (DCM) needs to be responsible for the increasing morbidity and mortality in diabetic patients with heart failure. Unfortunately, the pathogenesis of DCM has yet to be elaborate. Here we investigate the important role of lncRNA-ZFAS1 in the pathological process of DCM associated with ferroptosis. Methods Microarray data analysis of DCM in the patients or mice model from GEO was presented that ZFAS1 was significantly upregulated, miR-150-5p and CCND2 were significantly downregulated. High glucose (HG)-treated cardiomyocytes and db/db mice were simulated DCM in vitro and in vivo. Ad-ZFAS1, Ad-sh-ZFAS1, mimic miR-150-5p, Ad-CCND2, Ad-sh-CCND2 were injected into mice model or transfected into HG-treated Cardiomyocytes to clarify whether ZFAS1 can regulate miR-150-5p and CCND2 on ferroptosis. Effect of ZFAS1 on the left ventricular myocardial tissues in db/db mice and HG-treated cardiomyocytes, ferroptosis and apoptosis was determined by Masson staining, immunohistochemical staining, western blot, MBB staining, immunofluorescence staining and JC-1staining. The relationship among ZFAS1, miR-150-5p, CCND2 was identified by dual luciferase reporter assay and RNA Pull-down assay. Results Inhibition of ZFAS1 led to the reduced collagen deposition, decreased cardiomyocytes apoptosis, ferroptosis and attenuated the DCM progress. ZFAS1 can sponge miR-150-5p to regulate CCND2 expression. Ad-sh-ZFAS1, miR-150-5p mimic and Ad-CCND2 transfection contributed to attenuate ferroptosis and DCM both in vitro and in vivo, while transfection Ad-ZFAS1could reverse the positive effect of miR-150-5p mimic and Ad-CCND2 both in vitro and in vivo. Conclusion lncRNA-ZFAS1 acted as a ceRNA to sponge miR-150-5p can regulate CCND2 to promote cardiomyocytes ferroptosis and developed DCM, and inhibition of ZFAS1 could be a promising therapeutic target for the treatment and prevention of DCM.

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“…This aims to decrease Ca 2+ reuptake to the SR, which leads to cytosolic Ca 2+ overload [ 81 ]. The studies indicate that Ca 2+ overloads cause cardiac dysfunction [ 81 ] and induce mitochondria-mediated apoptosis [ 97 ].…”

Section: Noncoding Rnasmentioning

confidence: 99%

LncRNAs in Cardiomyocyte Maturation: New Window for Cardiac Regenerative Medicine

Kay

Soltani

2021

ncRNA

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Cardiomyocyte (CM) maturation, which is characterized by structural, functional, and metabolic specializations, is the last phase of CM development that prepares the cells for efficient and forceful contraction throughout life. Over the past decades, CM maturation has gained increased attention due to the fact that pluripotent stem cell-derived CMs are structurally, transcriptionally, and functionally immature and embryonic-like, which causes a defect in cell replacement therapy. The current challenge is to discover and understand the molecular mechanisms, which control the CM maturation process. Currently, emerging shreds of evidence emphasize the role of long noncoding RNAs (lncRNAs) in regulating different aspects of CM maturation, including myofibril maturation, electrophysiology, and Ca2+ handling maturation, metabolic maturation and proliferation to hypertrophy transition. Here, we describe the structural and functional characteristics of mature CMs. Furthermore, this review highlights the lncRNAs as crucial regulators of different aspects in CM maturation, which have the potential to be used for mature CM production. With the current advances in oligonucleotide delivery; lncRNAs may serve as putative therapeutic targets to produce highly mature CMs for research and regenerative medicine.

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lncRNA-ZFAS1 induces mitochondria-mediated apoptosis by causing cytosolic Ca2+ overload in myocardial infarction mice model

Cited by 78 publications

References 26 publications

GDF11 inhibits cardiomyocyte pyroptosis and exerts cardioprotection in acute myocardial infarction mice by upregulation of transcription factor HOXA3

GDF11 inhibits cardiomyocyte pyroptosis and exerts cardioprotection in acute myocardial infarction mice by upregulation of transcription factor HOXA3

Inhibition of the Long non-coding RNA ZFAS1 attenuates pathogenic ferroptosis by sponging miR-150-5p to activate CCND2 against diabetic cardiomyopathy

LncRNAs in Cardiomyocyte Maturation: New Window for Cardiac Regenerative Medicine

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