Simultaneous Suppression of Multiple Programmed Cell Death Pathways by miRNA-105 in Cardiac Ischemic Injury

Sunhye Shin, Jung Won Choi, Hanbyeol Moon, Chang Youn Lee, Jun Hee Park, Jiyun Lee, Hyang Hee Seo, Gyoonhee Han, Soyeon Lim, Seahyoung Lee, Sang Woo Kim, Ki Chul Hwang

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4 Citations (Scopus)

Abstract

Recent studies have shown that several upstream signaling elements of apoptosis and necroptosis are closely associated with acute injury in the heart. In our study, we observed that miR-105 was notably dysregulated in rat hearts with myocardial infarction (MI). Thus, the purpose of this study was to test the hypothesis that miR-105 participates in the regulation of RIP3/p-MLKL- and BNIP3-dependent necroptosis/apoptosis in H9c2 cells and MI rat hearts. Our results show that the RIP3/p-MLKL necroptotic pathway and BNIP3-dependent apoptosis signaling are enhanced in H9c2 cells under hypoxic conditions, whereas, compared with these pathways in the controls, those in miR-105-treated H9c2 cells are suppressed. Mechanistically, we identified miR-105 as the miRNA directly suppressing the expression of RIP3 and BNIP3, two important mediators involved in cell necroptosis and apoptosis. Furthermore, MI rat hearts injected with miR-105 had decreased infarct sizes, indicating that miR-105 is among three miRNAs that function simultaneously to suppress necroptotic/apoptotic cell death pathways and to inhibit MI-induced cardiomyocyte cell death at multiple levels. Taken together, miR-105 may constitute a new therapeutic strategy for cardioprotection in ischemic heart disease.

Original languageEnglish
Pages (from-to)438-449
Number of pages12
JournalMolecular Therapy - Nucleic Acids
Volume14
DOIs
Publication statusPublished - 2019 Mar 1

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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    Shin, S., Choi, J. W., Moon, H., Lee, C. Y., Park, J. H., Lee, J., Seo, H. H., Han, G., Lim, S., Lee, S., Kim, S. W., & Hwang, K. C. (2019). Simultaneous Suppression of Multiple Programmed Cell Death Pathways by miRNA-105 in Cardiac Ischemic Injury. Molecular Therapy - Nucleic Acids, 14, 438-449. https://doi.org/10.1016/j.omtn.2018.12.015