Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital heart disease (CHD) is the most common type of birth defect, but its underlying molecular mechanisms remain unidentified. Previous studies determined that Homo sapiens LYR motif containing 1 (LYRM1) is a novel nucleoprotein expressed at the highest level in adipose tissue and in high levels in heart tissue. The LYRM1 gene may play an important role in the development of the human heart. This study was designed to identify the biological characteristics of the LYRM1 gene in heart development. On the basis of expression-specific differentiation markers identified with quantitative real-time RT-PCR and the morphology of LYRM1-overexpressing cells during differentiation, ectopic expression was not found to significantly affect differentiation of P19 cells into cardiomyocytes. MTT assays and cell cycle analysis showed that LYRM1 dramatically increases the proliferation of P19 cells. Furthermore, data from annexin V-FITC binding and caspase-3 activity revealed that LYRM1 can inhibit the apoptosis of P19 cells. Our data suggest that LYRM1 might have the potential to modulate cell growth, apoptosis, and heart development.
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PMID:LYRM1, a gene that promotes proliferation and inhibits apoptosis during heart development. 2093 7

Congenital heart disease (CHD) is the most common type of human innate malformation in fetuses. LncRNAs have been pointed to play critical regulatory roles in various types of cardiac development and diseases including CHD. Our study aimed to explore the effects of lncRNA forkhead box D3 antisense RNA 1 (FOXD3-AS1) on hypoxia-induced injury in AC16 cardiomyocytes and the related molecular mechanism. In vitro cell model of CHD was established by stimulating AC16 cells with hypoxia (1% O2). Expression of FOXD3-AS1 and miR-150-5p was detected by qRT-PCR. Hypoxia-induced injury was evaluated by detecting cell survival, lactate dehydrogenase (LDH) release, apoptosis, and caspase-3/7 activity using MTT, LDH assay, flow cytometry analysis, and caspase-3/7 activity assay, respectively. The regulatory relationship between FOXD3-AS1 and miR-150-5p was explored by luciferase reporter assay, RNA immunoprecipitation (RIP), and qRT-PCR. Results showed that hypoxia exposure caused an upregulation of FOXD3-AS1 and a downregulation of miR-150-5p in AC16 cells. Knockdown of FOXD3-AS1 attenuated reduction of cell survival and increase of LDH release, apoptosis, caspase-3/7 activity, and Bcl-2 associated X (Bax) expression induced by hypoxia in AC16 cells. Notably, we demonstrated that FOXD3-AS1 directly interacted with miR-150-5p to inhibit its expression. miR-150-5p knockdown reinforced the reduction of survival and induction of apoptosis by hypoxia and attenuated the effects of FOXD3-AS1 silencing on the same parameters in AC16 cells. In conclusion, FOXD3-AS1 knockdown protected AC16 cardiomyocytes from hypoxia-induced injury by increasing cell survival and inhibiting apoptosis through upregulating miR-150-5p.
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PMID:FOXD3-AS1 Knockdown Suppresses Hypoxia-Induced Cardiomyocyte Injury by Increasing Cell Survival and Inhibiting Apoptosis via Upregulating Cardioprotective Molecule miR-150-5p In Vitro. 3297 15

Congenital heart disease (CHD) has severe morbidity and mortality worldwide. Evidence suggests that circularRNAs (circRNAs) are involved in the pathogenesis of human CHD. However, the regulatory mechanism remains uncertain. This study aimed to explore that mechanism. The levels of circular RNA MGAT1 (circMGAT1) and miR-34a were measured by quantitative polymerase chain reaction (qRT-PCR). Expression of yes-associated protein isoform 1 (YAP1) was assessed by western blot. Caspase-3 activity was evaluated by Caspase 3 Activity Assay Kit. CCK-8 assay was carried out to detect cell proliferation of hypoxia-induced AC16 cells. Cell apoptosis was analyzed by flow cytometry. In addition, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the relationship between miR-34a and circMGAT1 or YAP1 in vitro. The level of circMGAT1 was downregulated, while miR-34a was strikingly increased in CHD tissues and hypoxia-induced AC16 cells. CircMGAT1 was a sponge of miR-34a, and circMGAT1 targeted miR-34a to regulate cell proliferation and apoptosis in hypoxia-induced cardiomyocytes. Dual-luciferase reporter and RIP-assay verified that miR-34a directly targeted YAP1, and the expression of YAP1 was significantly suppressed by miR-34a mimics but was enhanced by miR-34a inhibitor. Interestingly, YAP1 restored the effect of miR-34a on cell proliferation and apoptosis in hypoxia-induced AC16 cells. Besides, circMGAT1 sponged miR-34a to regulate the expression of YAP1. In conclusion, circMGAT1 inhibited cell apoptosis and enhanced cell proliferation by regulating the miR-34a/YAP1 axis, providing a therapy target for the treatment of human CHD.
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PMID:Circular RNA MGAT1 regulates cell proliferation and apoptosis in hypoxia-induced cardiomyocytes through miR-34a/YAP1 axis. 3316 36