microRNA-99a Reduces Lipopolysaccharide-Induced Oxidative Injury by Activating Notch Pathway in H9c2 Cells

Jing, Ran; Zhou, Zhengming; Feng, Ke; Huang, Lei; Li, Chuanchang

doi:10.1536/ihj.16-261

Cited by 21 publications

(26 citation statements)

References 41 publications

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“…5,6 The miRNA biogenesis pathway is closely connected with heart functions and is involved in regulating angiogenesis, 7 heart development, 8 heart failure, 9 and ischemia reperfusion-injury (IRI). 10 According to the GSE74205 data analysis, miR-496 is significantly upregulated in rat cardiomyocytes, within 10 days of birth. For example, miR-99a has a positive effect, as it improves heart function in patients with AMI.…”

Section: Introductionmentioning

confidence: 99%

miR‐496 remedies hypoxia reoxygenation–induced H9c2 cardiomyocyte apoptosis via Hook3‐targeted PI3k/Akt/mTOR signaling pathway activation

Jin

Ni²

2019

J of Cellular Biochemistry

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The hypoxia‐reoxygenation (H/R) model helps analyze myocardial infarction triggered by acute myocardial ischemia, which induces cardiomyocyte proliferation and apoptosis. The Gene Expression Omnibus database was used to obtain the GSE74205 and GSE3866 microarray data, including microRNA (miRNA) and messenger RNA profiles, to catalog potential key miRNAs and genes. The role of rno‐mir‐496 expression in cardiomyocyte proliferation within 10 days of birth was established. The microRNA Target Prediction Database (miRDB) database—via Gene Ontology annotation—predicted hook microtubule tethering protein 3 (Hook3), a key target gene of rno‐mir‐496, was closely related to cell proliferation. Upregulation of miR‐496 related to a significant reduction in apoptosis of H9c2 and human cardiomyocytes treatment with H/R. Moreover, transfection of H9c2 cells with miR‐496 mimics, which were pretreated with H/R for 12 hours, increased Ki67 levels, proliferating cell nuclear antigen and Bcl‐2 proteins; and decreased cleaved caspase‐3 and Bax protein levels, as determined by reverse transcription‐polymerase chain reaction and Western blot assays. A dual‐luciferase reporter system confirmed that miR‐496 targets the Hook3 suppressor. Hook3 overexpression stimulated apoptosis in H/R‐treated cells, thus reducing cell proliferation. Upregulated miR‐496 activated phosphatidylinositol‐3‐kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling, while Hook3 exhibited the inverse trend in H/R‐treated H9c2 cells. In summary, with Hook3 functionality's aid, miR‐496 upregulation defends cells from H/R‐induced apoptosis and stimulates cell proliferation. miR‐496 targets Hook3 to trigger the PI3K/Akt/mTOR signaling pathway for antiapoptotic and proliferative effects.

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Section: Introductionmentioning

confidence: 99%

miR‐496 remedies hypoxia reoxygenation–induced H9c2 cardiomyocyte apoptosis via Hook3‐targeted PI3k/Akt/mTOR signaling pathway activation

Jin

Ni²

2019

J of Cellular Biochemistry

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“…# P < 0.05, ## P < 0.01, ### P < 0.001 versus sh-DIGIT + inhibitor NC group. signaling pathways: Given that PI3K/AKT and Notch signaling pathways are known to play key roles in numerous cellular functions including proliferation, migration, survival, and angiogenesis, [22][23][24] we focused on these two signaling pathways to further reveal the underling mechanism(s) via which Bmi-1 influenced the tube-formation capacity of HMEC-1 cells. Western blot analysis results showed that p-PI3K, p-AKT, Notch1, Notch2, and Notch3 were all downregulated in Bmi-1 suppressing-cells, while the same p-PI3K, p-AKT, Notch1, Notch2, and Notch3 were upregulated in Bmi-1 overexpressing-cells (Figure 7 A, B).…”

Section: Mir-134 Suppression Abolished Digit Silencediminished Cell Gmentioning

confidence: 99%

LncRNA DIGIT Accelerates Tube Formation of Vascular Endothelial Cells by Sponging miR-134

et al. 2018

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Atherosclerosis is one of the most prevalent and important cardiac diseases, involving the heart and brain. This study aimed to explore the impacts of lncRNA Divergent to GSC induced by TGF-b family signaling (DIGIT) on vascular endothelial cells tube-formation capacity so as to reveal the potentials of DIGIT in atherosclerosis therapy. DIGIT expression in human microvascular endothelial HMEC-1 cells was silenced by transfection with shRNAs-targeted DIGIT. The effects of DIGIT silence on cell viability, migration, apoptosis, and tube formation were then assessed. Additionally, the cross-regulation between DIGIT and miR-134, and between miR-134 and Bmi-1 was detected to further reveal through which mechanism (s) DIGIT mediated HMEC-1 cells. The results showed that DIGIT silence significantly reduced cell viability, migration, tube-like structures formation, and induced apoptosis in HMEC-1 cells. DIGIT worked as a sponge for miR-134, and the anti-growth, anti-migratory, and anti-tube-formation functions of DIGIT silence on HMEC-1 cells were abolished by miR-134 suppression. Bmi-1 was a target of miR-134, and Bmi-1 upregulation abolished miR-134 overexpression-diminished cell growth, migration, and tube formation of HMEC-1 cells. Furthermore, Bmi-1 upregulation activated PI3K/AKT and Notch signaling pathways. In conclusion, our study demonstrated that lncRNA DIGIT accelerated tube formation of vascular endothelial cells through sponging miR-134. Our findings suggest that DIGIT and miR-134 may be promising molecular targets for atherosclerosis therapy.

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“…12,13) In this issue, Jing and colleagues have provided evidence that miR-99a attenuates lipopolysaccharide (LPS)-induced oxidative injury in rat cardiomyocyte H9c2 cells. 14) MiRNAs are endogenous, small (approximately 18-25 nucleotides in length), non-protein-coding RNAs, present in almost all organisms. MicroRNAs inhibit mRNA expression post-transcriptionally by binding to the 3'-UTR of their target mRNAs.…”

Section: Article P422mentioning

confidence: 99%

“…16,17) Jing and colleagues demonstrated that transfecting H9c2 cells with miR-99a mimic prevented LPS-induced apoptotic cell death, which was associated with a decrease in ROS generation. 14) Conversely, transfection with miR-99a inhibitor enhanced LPS-induced ROS generation and cell death. Mechanistically, activation of Notch signaling might participate in cardioprotection induced by miR-99a, because miR-99a mimic induced activation of Notch 1 and Notch 2 and increased JAG1 expression, while miR-99a inhibitor had the opposite effects.…”

Section: Article P422mentioning

confidence: 99%

“…34) The study of Jing and colleagues 14) provides promising, albeit not definitive, evidence that miR99a joins the ranks of "cardioprotective miRNAs". Further studies are required to explore the more precise mechanism and function of miR-99a-mediated cardioprotection, and ultimately, to develop miR-99a-based therapeutics against oxidative injury in cardiovascular diseases.…”

Section: Article P422mentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA-99a

Liu

Akazawa

2017

Int. Heart J.

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R eactive oxygen species (ROS) are continuously formed in myocardium as a byproduct of mitochondrial oxidative phosphorylation, and are also produced by several enzymes such as NADPH oxidases, xanthine oxidase, and uncoupled endothelial NO synthase.1,2) In normal cardiovascular physiology, ROS act as essential signaling molecules that modulate the activity of many bioactive molecules including protein kinases, phosphatases, transcription factors, and cytoskeletal proteins.3) However, excessive and aberrant production of ROS during pathological oxidative stress can cause cellular dysfunction and death by inducing irreversible damage of organelles and macromolecules such as lipids, proteins, and DNA.1,2) An increasing body of evidence has suggested that oxidative stress is crucially involved in the pathogenesis and progression of a wide range of cardiovascular diseases.1,2) For example, it was reported that the myocardial ROS levels were elevated in animal models of ischemia-reperfusion injury 2,4) and heart failure, 5) and that a number of antioxidant strategies using ROS scavengers provided cardioprotection in these animal models.2) However, clinical interventions by treatment with antioxidants have proven to be ineffective or even harmful for patients with cardiovascular diseases.2,6) Rather than simple antioxidant strategies, a strategy to reduce pathological oxidative stress without altering physiological ROS signaling will put forward the translation of ROS modulation into the clinic. 7)

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microRNA-99a Reduces Lipopolysaccharide-Induced Oxidative Injury by Activating Notch Pathway in H9c2 Cells

Cited by 21 publications

References 41 publications

miR‐496 remedies hypoxia reoxygenation–induced H9c2 cardiomyocyte apoptosis via Hook3‐targeted PI3k/Akt/mTOR signaling pathway activation

miR‐496 remedies hypoxia reoxygenation–induced H9c2 cardiomyocyte apoptosis via Hook3‐targeted PI3k/Akt/mTOR signaling pathway activation

LncRNA DIGIT Accelerates Tube Formation of Vascular Endothelial Cells by Sponging miR-134

MicroRNA-99a

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