MiR-21 participates in the neuroprotection of diazoxide against hypoxic-ischemia encephalopathy by targeting PDCD4

ABSTRACT

Background

Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of neonatal death and permanent neurological disability. Here, we designed to quest therapeutic effects of diazoxide (DZ) on HIE and its mechanism.

Methods

The cell model of HIE was established. CCK8 and flow cytometry were applied to test cell viability and apoptosis. RT-qPCR and western blotting was evaluated to the expression of miR-21, PDCD4, PI3K, and p-AKT/AKT. Commercial kits were employed to detect SOD, MDA, LDH. DCFH-DA was used to measure intracellular ROS. ELISA was performed to estimate IL-1β, IL-6 and TNF-α. Dual-luciferase reporter gene and RIP assay were applied to confirm the binding relationships between miR-21 and PDCD4.

Results

In H19-7 cells and PC12 cells stimulated by OGD, with low cell viability, high apoptosis, miR-21 high expression and PDCD4 low expression. However, the functions were all reversed by DZ administration. Furthermore, miR-21 inhibitor could abolish the beneficial effects of DZ on OGD-induced cells. Besides, miR-21 could interact with PDCD4. In addition, PDCD4 involved with the regulation of DZ to OGD-induced cells via PI3K/AKT pathway.

Conclusion

DZ enhanced miR-21 level and inhibited PDCD4 level via PI3K/AKT pathway to resisted HIE.

KEYWORDS:

• Diazoxide
• miR-21
• PDCD4
• HIE
• PI3K/AKT

Disclosure statement

These authors declared no competing interests in this work.

Additional information

Funding

This work was supported by Basic Research Project of Shenzhen Science and Technology Innovation Committee (No. JCYJ20190808154015736) and District-level scientific research project of medical and health institutions in Longhua district of Shenzhen .