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

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

  • Mol Med Rep. 2021 Feb;23(2):116. doi: 10.3892/mmr.2020.11755.
Jiong Li  # 1 Jing Xie  # 2 Yan-Zhen Wang 3 Yi-Rong Gan 3 Ling Wei 4 Guan-Waner Ding 5 Yan-Hong Ding 6 Ding-Xiong Xie 3
Affiliations

Affiliations

  • 1 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
  • 2 Department of Ultrasonic Diagnosis, The First People's Hospital of Lanzhou, Lanzhou, Gansu 730050, P.R. China.
  • 3 Gansu Cardiovascular Institute, Lanzhou, Gansu 730050, P.R. China.
  • 4 Outpatient Department, The First People's Hospital of Lanzhou, Lanzhou, Gansu 730050, P.R. China.
  • 5 Medical Department, Shijiazhuang People's Medical College, Shijiazhuang, Hebei 050599, P.R. China.
  • 6 Anesthesiology Department, The First People's Hospital of Lanzhou, Lanzhou, Gansu 730050, P.R. China.
  • # Contributed equally.
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.

Keywords

apoptosis; cardiomyocytes; endoplasmic reticulum stress; long non-coding RNA discrimination antagonizing non-protein coding RNA; myocardial infarction.

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