PMID- 32674625
OWN - NLM
STAT- MEDLINE
DCOM- 20220113
LR  - 20231031
IS  - 1532-4311 (Electronic)
IS  - 0882-0139 (Linking)
VI  - 50
IP  - 8
DP  - 2021 Nov
TI  - Overexpression of lncRNA HULC Attenuates Myocardial Ischemia/reperfusion Injury 
      in Rat Models and Apoptosis of Hypoxia/reoxygenation Cardiomyocytes via Targeting 
      miR-377-5p through NLRP3/Caspase‑1/IL‑1beta Signaling Pathway Inhibition.
PG  - 925-938
LID - 10.1080/08820139.2020.1791178 [doi]
AB  - OBJECTIVE: Acute myocardial infarction (AMI) is characterized by myocardial 
      tissue necrosis and activation of inflammatory response. This study aims to 
      elucidate the potential mechanism underlying the protective effects of long 
      non-coding RNA (lncRNA) highly up-regulated in liver cancer (HULC) against 
      myocardial ischemia/reperfusion (I/R) injury in rat models and apoptosis of 
      cardiomyocytes. METHODS: We firstly established rat models of myocardial I/R 
      injury and rat cardiomyocyte (H9c2 cells) models of hypoxia/reoxygenation (H/R) 
      injury. Sprague-Dawley (SD) neonatal rats were randomized into four groups: sham, 
      I/R, I/R+ microRNA (miR) -377-5p mimic, and I/R+ miR-377-5p antagomir, 
      respectively. Then, histopathological examination was applied. Apoptosis was 
      evaluated by transferase-mediated dUTP nick end labeling (TUNEL) staining. Cell 
      vitality was measured using MTT assay. The concentrations of creatine kinase MB 
      (CK-MB), cardiac troponin I (cTnI), interleukin (IL) -6 (IL-6), and tumor 
      necrosis factor-alpha (TNF-alpha) were detected by enzyme-linked immunosorbent assay 
      (ELISA). The expression of Cleaved-Caspase-3, Caspase-3, NOD-like receptor P3 
      (NLRP3), Caspase-1, and IL-1beta was analyzed by immunohistochemical (IHC) or 
      Western blot analysis. RESULTS: We found that HULC was downregulated and 
      miR-377-5p was upregulated in IR-injured myocardial tissue and the H/R-induced 
      H9c2 cell. Overexpression of miR-377-5p increased myocardial dysfunction and 
      apoptosis and activated formation and secretion of IL-6 and TNF-alpha. The 
      preprocessing of miR-377-5p silencing emerged opposite results. Strikingly, dual 
      luciferase reporter assay showed that HULC was a sponge of miR-377-5p. 
      Subsequently, mechanism experiments revealed that NLRP3/Caspase‑1/IL‑1beta was a 
      target axis of miR-377-5p. In vitro, the protective effect of HULC overexpression 
      on H9c2 cell viability and inflammation was offset by miR-377-5p silencing. 
      Finally, rescue assay suggested that HULC-miR-377-5p -NLRP3/Caspase‑1/IL‑1beta axis 
      regulated the apoptosis and inflammation of H/R-induced H9c2 cells. CONCLUSIONS: 
      Overall, these results indicate that the protective effect of HULC against 
      myocardial I/R injury and H/R cardiomyocyte apoptosis partially relies on the 
      inhibition of NLRP3/Caspase‑1/IL‑1beta signaling pathway.
FAU - Liang, Huiqing
AU  - Liang H
AD  - Department of Cardiology, The First Affiliated Hospital of Hebei North 
      University, Zhangjiakou, China.
FAU - Li, Fangjiang
AU  - Li F
AD  - Department of Cardiology, The First Affiliated Hospital of Hebei North 
      University, Zhangjiakou, China.
FAU - Li, Huixian
AU  - Li H
AD  - Department of Cardiology, The First Affiliated Hospital of Hebei North 
      University, Zhangjiakou, China.
FAU - Wang, Rui
AU  - Wang R
AD  - Department of Cardiology, The First Affiliated Hospital of Hebei North 
      University, Zhangjiakou, China.
FAU - Du, Meiling
AU  - Du M
AD  - Department of Cardiology, The First Affiliated Hospital of Hebei North 
      University, Zhangjiakou, China.
LA  - eng
PT  - Journal Article
DEP - 20200717
PL  - England
TA  - Immunol Invest
JT  - Immunological investigations
JID - 8504629
RN  - 0 (MIRN377 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, rat)
RN  - 0 (RNA, Long Noncoding)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Caspase 1
MH  - Hypoxia
MH  - *MicroRNAs/genetics
MH  - *Myocardial Reperfusion Injury/genetics
MH  - Myocytes, Cardiac
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/genetics
MH  - *RNA, Long Noncoding/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
OTO - NOTNLM
OT  - HULC
OT  - hypoxia/reoxygenation myocardial cell
OT  - miR-377-5p
OT  - myocardial apoptosis
OT  - myocardial ischemia-reperfusion
EDAT- 2020/07/18 06:00
MHDA- 2022/01/14 06:00
CRDT- 2020/07/18 06:00
PHST- 2020/07/18 06:00 [pubmed]
PHST- 2022/01/14 06:00 [medline]
PHST- 2020/07/18 06:00 [entrez]
AID - 10.1080/08820139.2020.1791178 [doi]
PST - ppublish
SO  - Immunol Invest. 2021 Nov;50(8):925-938. doi: 10.1080/08820139.2020.1791178. Epub 
      2020 Jul 17.