1. Academic Validation
  2. LncRNA H19 Aggravates Cerebral Ischemia/Reperfusion Injury by Functioning as a ceRNA for miR-19a-3p to Target PTEN

LncRNA H19 Aggravates Cerebral Ischemia/Reperfusion Injury by Functioning as a ceRNA for miR-19a-3p to Target PTEN

  • Neuroscience. 2020 Jun 15;437:117-129. doi: 10.1016/j.neuroscience.2020.04.020.
Ning Gao 1 Hong Tang 1 Ling Gao 1 Guo-Long Tu 1 Han Luo 1 Ying Xia 2
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Affiliated Haikou Hospital at Xiangya Medical College, Central South University, Haikou 570208, Hainan Province, People's Republic of China.
  • 2 Department of Neurosurgery, Affiliated Haikou Hospital at Xiangya Medical College, Central South University, Haikou 570208, Hainan Province, People's Republic of China. Electronic address: [email protected].
Abstract

Long non-coding RNAs (lncRNAs) play critical roles in regulating the progression of cerebral ischemia. LncRNA H19 was significantly up-regulated under ischemia-reperfusion (I/R) damage and implicatedin I/R injury progression, but the mechanisms remain unclear. Mice were subjected to middle cerebral artery occlusion (MCAO)/R (1 h/24 h) to build an I/R injury model and the infarct volume and neurological deficit were assessed. Human neuroblastoma cell line SH-SY5Y was used in oxygen-glucose deprivation and reperfusion (OGD/R, 3 h/24 h) injury model. Expression of genes were evaluated by qRT-PCR or western blotting. Flow cytometry and TUNEL were performed to examine Apoptosis. Cell viability was determined with CCK8 assay. LDH, MDA, SOD levels were evaluated using commercial detection kits. Furthermore, dual luciferase reporter assay was conducted to confirm the binding between H19 and miR-19a-3p, as well miR-19a-3p and PTEN. The results showed that H19 was up-regulated whereas miR-19a-3p was down-regulated in I/R tissues and OGD/R induced cells. H19 aggravated I/R or OGD/R caused oxidative stress and Apoptosis via PTEN/Akt signaling pathway. H19 regulated PI3K/AKTsignaling through acting as a ceRNA for miR-19a-3p to target PTEN. H19 knockdown and miR-19a-3p overexpression relieved I/R or OGD/R induced neuronal cell oxidative stress and Apoptosis. H19/miR-19a-3p/PTEN axis could promote cerebral I/R injury via PI3K/Akt pathway. These demonstrated a mechanism how H19 participates in I/R injury, and provided us a potential target for I/R injury diagnosis and treatment.

Keywords

AKT; PTEN; cerebral ischemia/reperfusion injury; lncRNA H19; miR-19a-3p.

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