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Overexpression of lncRNA Dancr inhibits apoptosis and enhances autophagy to protect cardiomyocytes from endoplasmic reticulum stress injury via sponging microRNA-6324

  • Authors:
    • Jiong Li
    • Jing Xie
    • Yan-Zhen Wang
    • Yi-Rong Gan
    • Ling Wei
    • Guan-Waner Ding
    • Yan-Hong Ding
    • Ding-Xiong Xie
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of Ultrasonic Diagnosis, The First People's Hospital of Lanzhou, Lanzhou, Gansu 730050, P.R. China, Gansu Cardiovascular Institute, Lanzhou, Gansu 730050, P.R. China, Outpatient Department, The First People's Hospital of Lanzhou, Lanzhou, Gansu 730050, P.R. China, Medical Department, Shijiazhuang People's Medical College, Shijiazhuang, Hebei 050599, P.R. China, Anesthesiology Department, The First People's Hospital of Lanzhou, Lanzhou, Gansu 730050, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 116
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    Published online on: December 3, 2020
       https://doi.org/10.3892/mmr.2020.11755
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Abstract

Endoplasmic reticulum stress (ERS) contributes to the pathogenesis of myocardial ischemia/reperfusion injury and myocardial infarction (MI). Long non-coding RNAs (lncRNAs) serve an important role in cardiovascular diseases, and lncRNA discrimination antagonizing non-protein coding RNA (Dancr) alleviates cardiomyocyte damage. microRNA (miR)-6324 was upregulated in MI model rats and was predicted to bind to Dancr. The present study aimed to investigate the role of Dancr in ERS-induced cardiomyocytes and the potential underlying mechanisms. Tunicamycin (Tm) was used to induce ERS. Cell viability, apoptosis and levels of associated proteins, ERS and autophagy in Dancr-overexpression H9C2 cells and miR-6234 mimic-transfected H9C2 cells were assessed using Cell Counting Kit-8, TUNEL staining and western blot assay, respectively. The results suggested that Dancr expression levels and cell viability were downregulated by Tm in a concentration-dependent manner compared with the control group. Tm induced apoptosis, ERS and autophagy, as indicated by an increased ratio of apoptotic cells, increased expression levels of Bax, cleaved (c)-caspase-3/9, glucose-regulated protein 78 kDa (GRP78), phosphorylated (p)-inositol-requiring enzyme-1α (IRE1α), spliced X-box-binding protein 1 (Xbp1s), IRE1α, activating transcription factor (ATF)6, ATF4, Beclin 1 and microtubule associated protein 1 light chain 3α (LC3)II/I, and decreased expression levels of Bcl-2, unspliced Xbp1 (Xbp1u) and p62 in the Tm group compared with the control group. Moreover, the results indicated that compared with the Tm + overexpression (Oe)-negative control (NC) group, the Tm + Oe-Dancr group displayed decreased apoptosis, but enhanced ERS and autophagy to restore cellular homeostasis. Compared with the Tm + Oe-NC group, the Tm + Oe-Dancr group decreased the ratio of apoptotic cells, decreased expression levels of Bax, c-caspase-3/9 and Xbp1u, and increased expression levels of Bcl-2, p-IRE1α, Xbp1s, Beclin 1 and LC3II/I. Dancr overexpression also significantly downregulated miR-6324 expression compared with Oe-NC. The dual-luciferase reporter assay further indicated an interaction between Dancr and miR-6324. In addition, miR-6324 mimic partially reversed the effects of Dancr overexpression on Tm-induced apoptosis, ERS and autophagy. In conclusion, lncRNA Dancr overexpression protected cardiomyocytes against ERS injury via sponging miR-6324, thus inhibiting apoptosis, enhancing autophagy and restoring ER homeostasis.
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Copy and paste a formatted citation
Spandidos Publications style
Li J, Xie J, Wang Y, Gan Y, Wei L, Ding G, Ding Y and Xie D: Overexpression of lncRNA Dancr inhibits apoptosis and enhances autophagy to protect cardiomyocytes from endoplasmic reticulum stress injury via sponging microRNA-6324. Mol Med Rep 23: 116, 2021.
APA
Li, J., Xie, J., Wang, Y., Gan, Y., Wei, L., Ding, G. ... Xie, D. (2021). Overexpression of lncRNA Dancr inhibits apoptosis and enhances autophagy to protect cardiomyocytes from endoplasmic reticulum stress injury via sponging microRNA-6324. Molecular Medicine Reports, 23, 116. https://doi.org/10.3892/mmr.2020.11755
MLA
Li, J., Xie, J., Wang, Y., Gan, Y., Wei, L., Ding, G., Ding, Y., Xie, D."Overexpression of lncRNA Dancr inhibits apoptosis and enhances autophagy to protect cardiomyocytes from endoplasmic reticulum stress injury via sponging microRNA-6324". Molecular Medicine Reports 23.2 (2021): 116.
Chicago
Li, J., Xie, J., Wang, Y., Gan, Y., Wei, L., Ding, G., Ding, Y., Xie, D."Overexpression of lncRNA Dancr inhibits apoptosis and enhances autophagy to protect cardiomyocytes from endoplasmic reticulum stress injury via sponging microRNA-6324". Molecular Medicine Reports 23, no. 2 (2021): 116. https://doi.org/10.3892/mmr.2020.11755
Copy and paste a formatted citation
x
Spandidos Publications style
Li J, Xie J, Wang Y, Gan Y, Wei L, Ding G, Ding Y and Xie D: Overexpression of lncRNA Dancr inhibits apoptosis and enhances autophagy to protect cardiomyocytes from endoplasmic reticulum stress injury via sponging microRNA-6324. Mol Med Rep 23: 116, 2021.
APA
Li, J., Xie, J., Wang, Y., Gan, Y., Wei, L., Ding, G. ... Xie, D. (2021). Overexpression of lncRNA Dancr inhibits apoptosis and enhances autophagy to protect cardiomyocytes from endoplasmic reticulum stress injury via sponging microRNA-6324. Molecular Medicine Reports, 23, 116. https://doi.org/10.3892/mmr.2020.11755
MLA
Li, J., Xie, J., Wang, Y., Gan, Y., Wei, L., Ding, G., Ding, Y., Xie, D."Overexpression of lncRNA Dancr inhibits apoptosis and enhances autophagy to protect cardiomyocytes from endoplasmic reticulum stress injury via sponging microRNA-6324". Molecular Medicine Reports 23.2 (2021): 116.
Chicago
Li, J., Xie, J., Wang, Y., Gan, Y., Wei, L., Ding, G., Ding, Y., Xie, D."Overexpression of lncRNA Dancr inhibits apoptosis and enhances autophagy to protect cardiomyocytes from endoplasmic reticulum stress injury via sponging microRNA-6324". Molecular Medicine Reports 23, no. 2 (2021): 116. https://doi.org/10.3892/mmr.2020.11755
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