Long noncoding RNA C2dat1 protects H9c2 cells against hypoxia injury by downregulating miR-22.

Myocardial ischemia is accompanied with hypoxia injury in myocardial cells. Long noncoding RNAs (lncRNA) CAMK2D-associated transcript 1 (C2dat1) C2dat1) has been linked with several ischemic diseases. However, the investigation regarding its role in myocardial ischemia is relatively rare. The aim of this study was to examine the role of C2dat1 in hypoxia response in H9c2 cells. H9c2 cells were subjected to hypoxia to evoke cell damage. Expressions of C2dat1, miR-22, and VEGF in H9c2 cells were altered by transfection, and then cell survival, migration, and invasion were respectively assessed posttransfection. Regulatory relationship between C2dat1, miR-22, and VEGF, as well as the involvement of PI3K/AKT/mTOR and JAK/STAT3 pathways in H9c2 cells injury was then studied. C2dat1 upregulation ameliorated hypoxia injury in H9c2 cells due to the increased viability, migration, and invasion, as well as the decreased apoptosis. miR-22 was negatively regulated by C2dat1. The effects of C2dat1 on H9c2 cells injured by hypoxia were attenuated when miR-22 was overexpressed. VEGF was a target gene of miR-22, and VEGF exerted similar protective effects to C2dat1. Finally, we found that silence of C2dat1 deactivated PI3K/AKT/mTOR and JAK/STAT3 pathways via regulating miR-22 and its downstream gene VEGF. C2dat1-miR-22-VEGF axis could regulate hypoxia injury in H9c2 cells. C2dat1 alleviated hypoxia injury possibly via downregulating miR-22, then upregulating VEGF, which further enhancing the activation of PI3K/AKT/mTOR and JAK/STAT3 pathways.