Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1 (5-Year IF – 2.0)
Journal Citation Indicator (JCI) (2023) – 0.4
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Index Copernicus  – 171.00; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 6, June, p. 719–728

doi: 10.17219/acem/93878

Publication type: original article

Language: English

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Knockdown of long noncoding RNA Malat1 aggravates hypoxia-induced cardiomyocyte injury by targeting miR-217

Yuan Yao1,B,C,D,F, Xiaoying Fan1,B,C,D,F, Bo Yu1,B,D,F, Tianfa Li2,C,D,F, Yao Zhang1,A,D,E,F

1 Department of Cardiovascular Medicine, The 2nd Affiliated Hospital of Harbin Medical University, China

2 Department of Cardiovascular Medicine, The Affiliated Hospital of Hainan Medical College, Haikou, China

Abstract

Background. Expression of long noncoding (lncRNA) Malat1 can be increased by hypoxia in cardiomyocyte. Downregulation of Malat1 contributes to the reduction of cardiomyocyte apoptosis. However, the function of Malat1 in myocardial ischemia is unclear.
Objectives. This study investigated the functional role of lncRNA Malat1 in hypoxia-induced H9c2 cell injury.
Material and Methods. H9c2 cells were exposed to hypoxia treatment. Cell proliferation, migration, invasion, and apoptosis were detected using trypan blue exclusion assay, two-chamber migration/invasion assay, annexin V-FITC/PI staining, and western blotting, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to analyze the expression levels of Malat1. The effects of Malat1 knockdown on cell proliferation, migration, invasion, and apoptosis were also measured. The interaction between Malat1 and microRNA-217 (miR-217) as well as miR-217 and sirtuin 1 (Sirt1) were analyzed using a dual luciferase reporter assay and qRT-PCR. Effects of miR-217 and Sirt1 on hypoxia-induced H9c2 cell growth were assessed.
Results. Hypoxia induced H9c2 cell injury by inhibiting cell proliferation, migration and invasion, and by promoting apoptosis. Hypoxia significantly enhanced the expression of Malat1. Malat1 bound to miR-217 and Sirt1 was a direct target of miR-217. Knockdown of Malat1 aggravated hypoxia-induced H9c2 cell injury by overexpression of miR-217. Overexpression of Sirt1 alleviated H9c2 cell injury by activating phosphatidylinositol 3-kinase/protein kinase 3 (PI3K/AKT) and Notch signaling pathways.
Conclusion. These findings suggest that Malat1 exerted important roles in hypoxia-induced cardiomyocyte injury by regulating miR-217-mediated Sirt1 and downstream PI3K/AKT and Notch signaling pathways.

Key words

myocardial ischemia, Malat1, hypoxia-induced cell injury, microRNA-217, sirtuin 1

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