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Article

Downregulation of microRNA‑199a‑5p protects cardiomyocytes in cyanotic congenital heart disease by attenuating endoplasmic reticulum stress

  • Authors:
    • Yang Zhou
    • Wei‑Kun Jia
    • Zhao Jian
    • Liang Zhao
    • Chen‑Cheng Liu
    • Yong Wang
    • Ying‑Bin Xiao
  • View Affiliations / Copyright

    Affiliations: Department of Cardiovascular Surgery, Xinqiao Hospital of The Third Military Medical University, Chongqing 400037, P.R. China
  • Pages: 2992-3000
    |
    Published online on: July 6, 2017
       https://doi.org/10.3892/mmr.2017.6934
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Abstract

Chronic hypoxia is a key pathological change in patients with cyanotic congenital heart defect (CCHD). It has been demonstrated that enhanced myocardial unfolded protein response (UPR) increases the capacity to buffer endoplasmic reticulum (ER) stress and to avoid subsequent apoptosis caused by the hypoxia that underlies CCHD. The present study was performed to determine the regulatory role of microRNAs (miRNAs) in this cytoprotective UPR process. The results revealed that miR‑199a‑5p was markedly downregulated in the cardiac tissue of patients with CCHD and in human myocardial cells cultured in hypoxic conditions. The two major UPR modulators, 78 kDa glucose‑regulated protein (GRP78) and activating transcription factor 6 (ATF6), were potential target genes of miR‑199a‑5p in CCHD myocardial specimens. In addition, the miR‑199a‑5p mimic and inhibitor were evidently able to change GRP78 and ATF6 gene expression and ER stress‑associated apoptosis in hypoxia‑treated cardiomyocytes. The interaction between miR‑199a‑5p and the ATF6 and GRP78 3'‑UTR binding sites in myocardial cells was also confirmed by luciferase assay. Thus, it is concluded that myocardial downregulation of miR‑199a‑5p favors the UPR against hypoxia‑induced ER stress in CCHD, which contributes to myocardial protection.
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Copy and paste a formatted citation
Spandidos Publications style
Zhou Y, Jia WK, Jian Z, Zhao L, Liu CC, Wang Y and Xiao YB: Downregulation of microRNA‑199a‑5p protects cardiomyocytes in cyanotic congenital heart disease by attenuating endoplasmic reticulum stress. Mol Med Rep 16: 2992-3000, 2017.
APA
Zhou, Y., Jia, W., Jian, Z., Zhao, L., Liu, C., Wang, Y., & Xiao, Y. (2017). Downregulation of microRNA‑199a‑5p protects cardiomyocytes in cyanotic congenital heart disease by attenuating endoplasmic reticulum stress. Molecular Medicine Reports, 16, 2992-3000. https://doi.org/10.3892/mmr.2017.6934
MLA
Zhou, Y., Jia, W., Jian, Z., Zhao, L., Liu, C., Wang, Y., Xiao, Y."Downregulation of microRNA‑199a‑5p protects cardiomyocytes in cyanotic congenital heart disease by attenuating endoplasmic reticulum stress". Molecular Medicine Reports 16.3 (2017): 2992-3000.
Chicago
Zhou, Y., Jia, W., Jian, Z., Zhao, L., Liu, C., Wang, Y., Xiao, Y."Downregulation of microRNA‑199a‑5p protects cardiomyocytes in cyanotic congenital heart disease by attenuating endoplasmic reticulum stress". Molecular Medicine Reports 16, no. 3 (2017): 2992-3000. https://doi.org/10.3892/mmr.2017.6934
Copy and paste a formatted citation
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Spandidos Publications style
Zhou Y, Jia WK, Jian Z, Zhao L, Liu CC, Wang Y and Xiao YB: Downregulation of microRNA‑199a‑5p protects cardiomyocytes in cyanotic congenital heart disease by attenuating endoplasmic reticulum stress. Mol Med Rep 16: 2992-3000, 2017.
APA
Zhou, Y., Jia, W., Jian, Z., Zhao, L., Liu, C., Wang, Y., & Xiao, Y. (2017). Downregulation of microRNA‑199a‑5p protects cardiomyocytes in cyanotic congenital heart disease by attenuating endoplasmic reticulum stress. Molecular Medicine Reports, 16, 2992-3000. https://doi.org/10.3892/mmr.2017.6934
MLA
Zhou, Y., Jia, W., Jian, Z., Zhao, L., Liu, C., Wang, Y., Xiao, Y."Downregulation of microRNA‑199a‑5p protects cardiomyocytes in cyanotic congenital heart disease by attenuating endoplasmic reticulum stress". Molecular Medicine Reports 16.3 (2017): 2992-3000.
Chicago
Zhou, Y., Jia, W., Jian, Z., Zhao, L., Liu, C., Wang, Y., Xiao, Y."Downregulation of microRNA‑199a‑5p protects cardiomyocytes in cyanotic congenital heart disease by attenuating endoplasmic reticulum stress". Molecular Medicine Reports 16, no. 3 (2017): 2992-3000. https://doi.org/10.3892/mmr.2017.6934
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