Long Non-coding RNA H19 Deteriorates Hypoxic-Ischemic Brain Damage by Interacting with MicroRNA-140-5p and STAT3

Abstract

Objective: Even though extensive studies have surveyed long non-coding RNA (lncRNA)-related networks in hypoxic-ischemic brain damage (HIBD), the concrete function of lncRNA H19 (H19) in HIBD is still in ambiguity. Therein, this work intends to decipher H19-related network of microRNA (miR)-140-5p and signal transducer and activator of transcription 3 (STAT3) in HIBD.

Methods: Brain microvascular endothelial cells (BMECs) from BALB/c mice were isolated and induced by oxygen glucose deprivation (OGD). OGD-induced BMECs were transfected with depleted or restored H19, miR-140-5p or STAT3, and cell apoptosis, migration and angiogenesis were examined. H19, miR-140-5p and STAT3 expression and their internal connections were tested.

Results: H19 and STAT3 were overexpressed while miR-140-5p was down-regulated in OGD-induced BMECs. H19 or STAT3 knockdown, or miR-140-5p restoration repressed apoptosis and improved migration and angiogenesis of OGD-induced BMECs. MiR-140-5p restoration negated the impacts of up-regulated H19 on OGD-induced BMECs. H19 bound to miR-140-5p to modulate STAT3 expression.

Conclusion: The work illustrates that depleting H19 or STAT3 or restoring miR-140-5p attenuates HIBD and supplies a novel perspective for HIBD management.

Keywords: Angiogenesis; Apoptosis; Hypoxic-ischemic brain damage; Long non-coding RNA H19; MicroRNA-140-5p; Migration; Oxygen glucose deprivation; Signal transducer and activator of transcription 3.