Molecules and Cells

  • 제45권6호
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  • Pages.403-412
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  • 2022
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Protective Role of miR-34c in Hypoxia by Activating Autophagy through BCL2 Repression

  • Kim, Soyoung (Department of Convergence Medicine & Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Han, Jaeseok (Department of Convergence Medicine & Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Ahn, Young-Ho (Department of Molecular Medicine, College of Medicine, Ewha Womans University) ;
  • Ha, Chang Hoon (Department of Convergence Medicine & Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Hwang, Jung Jin (Department of Convergence Medicine & Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Lee, Sang-Eun (Division of Cardiology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Jae-Joong (Division of Cardiology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Nayoung (Department of Convergence Medicine & Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine)
  • 투고 : 2021.10.28
  • 심사 : 2022.02.24
  • 발행 : 2022.06.30
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초록

Hypoxia leads to significant cellular stress that has diverse pathological consequences such as cardiovascular diseases and cancers. MicroRNAs (miRNAs) are one of regulators of the adaptive pathway in hypoxia. We identified a hypoxia-induced miRNA, miR-34c, that was significantly upregulated in hypoxic human umbilical cord vein endothelial cells (HUVECs) and in murine blood vessels on day 3 of hindlimb ischemia (HLI). miR-34c directly inhibited BCL2 expression, acting as a toggle switch between apoptosis and autophagy in vitro and in vivo. BCL2 repression by miR-34c activated autophagy, which was evaluated by the expression of LC3-II. Overexpression of miR-34c inhibited apoptosis in HUVEC as well as in a murine model of HLI, and increased cell viability in HUVEC. Importantly, the number of viable cells in the blood vessels following HLI was increased by miR-34c overexpression. Collectively, our findings show that miR-34c plays a protective role in hypoxia, suggesting a novel therapeutic target for hypoxic and ischemic diseases in the blood vessels.

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과제정보

This research was supported by Basic Science Research Program through National Research Foundation of Korea (NRF) funded by Ministry of Science and ICT (grant No. 2019R1A2C1008880) and by Ministry of Education (grant No. 2016R1D1A1B03933929).

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