MicroRNA-145 Aggravates Hypoxia-Induced Injury by Targeting Rac1 in H9c2 Cells

Abstract

Background/Aims: Myocardial infarction (MI) is a leading cause of morbidity and mortality. Here, we sought to explore the potential role and underlying mechanism of miR-145 in MI. Methods: H9c2 cells were cultured under persistent hypoxia to simulate MI. The hypoxia-induced injury was assessed on the basis of cell viability, migration, invasion and apoptosis. The expression of miR-145 was evaluated by qRT-PCR and the influence of aberrantly expressed miR-145 on H9c2 cells under hypoxia was also estimated. Utilizing bioinformatics methods, the target genes of miR-145 were verified by luciferase reporter assay. Then, effects of abnormally expressed target gene on miR-145 silenced H9c2 cells were assessed. Finally, the phosphorylation levels of key kinases in the phosphatidylinositol-3-kinase (PI3K)/AKT and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways were detected by Western blot analysis. Results: Hypoxia remarkably lowered viability, migration and invasion but promoted cell apoptosis. Meantime, the miR-145 level was up-regulated in H9c2 cells under hypoxia. Following experiments suggested that hypoxia-induced injury was exacerbated by miR-145 overexpression while was alleviated by miR-145 silence. Rac1 was predicted and further validated to be a target gene of miR-145. The influence of miR-145 silencing on H9c2 cells under hypoxia could be reversed by down-regulation of Rac1. Additionally, the phosphorylation levels of PI3K, AKT, MAPK and ERK were all elevated in miR-145 silenced cells and these alterations were reversed by down-regulation of Rac1. Conclusion: miR-145 silencing could protect H9c2 cells against hypoxia-induced injury by targeting Rac1, in which PI3K/AKT and MAPK/ERK pathways might be involved.

LncRNA MALAT1 up-regulates VEGF-A and ANGPT2 to promote angiogenesis in brain microvascular endothelial cells against oxygen–glucose deprivation via targettingmiR-145

“…To further uncover the underlying molecular mechanism of how lncRNA-MALAT1 regulated the expressions of VEGF-A and ANGPT2, the role of miR-145 was investigated in the present study. miR-145 was also confirmed to be up-regulated in BMECs that underwent OGD treatment, which is in-line with the recent finding [18]. This is the first time that miR-145 has been demonstrated to inhibit angiogenesis progress in BMECs treated by OGD in addition to showing its potential to attenuate cell proliferation.…”

“…Mounting studies suggest that miR-145 is up-regulated by hypoxia and facilitates hypoxia-induced cell injury [18]. Earlier findings on the suppressive role of miR-145 in angiogenesis through mediating the expressions of vascular endothelial growth factor (VEGF) and Angiopoietin-2 (ANGPT2) in cancers suggests that a possible regulatory pathway may exist in the physiological progress of ischemic stroke as well [19,20].…”

Long non-coding RNA ROR mitigates cobalt chloride-induced hypoxia injury through regulation of miR-145

“…For example, miR-145 alleviated lipopolysaccharides-induced inflammatory injury in human fibroblast-like synoviocyte MH7A cells [31]. By contrary, miR-145 was reported to promoted hypoxiainduced injury in H9c2 cells [32]. Combined previous studies and our own result, the roles of miR-145 various maybe because of different cell type and different treatments.…”

Identification and characterization of differentially expressed miRNAs in HepG2 cells under normoxic and hypoxic conditions

“…3 MiR-145 aggravates hypoxia induced injury via targeting Rac1 in H9c2 cells. 4 MiR-485 inhibits the malignant behavior of glioblastoma cells by targeting p21-activated kinase 4 (PAK4). 5 MiR-320 may regulate the development of autophagy by targeting HIF-1a in retinoblastoma under hypoxia conditions.…”