MicroRNA-21a-5p Promotes Cerebral Angiogenesis in Transient Ischemic Attack by Targeting RBMS3 and Subsequently Modulating the TGFBR1/SMAD2/3 Pathway.

AIMS: Transient ischemic attack (TIA) serves as a crucial precursor to a potential stroke. Angiogenesis is essential for the renovation of the damaged brain after TIA. This study aimed to elucidate the role of miRNA-21a-5p in angiogenesis following TIA and unravel the underlying mechanisms.

METHODS

In vivo and in vitro TIA models were established using the modified suture middle cerebral artery occlusion and oxygen-glucose deprivation/reoxygenation methods. Differentially expressed miRNAs in the TIA group versus the control group were identified using small RNA sequencing. The putative target genes of miRNA-21a-5p were predicted via bioinformatics analysis and validated using a dual luciferase reporter gene assay. TIA models were then treated with miRNA-21a-5p antagomir/agomir or/and an adeno-associated virus interfering with the target gene to assess the effects of miRNA-21a-5p and the identified target gene on angiogenesis after TIA.

RESULTS

MiRNA-21a-5p was the miRNA with the most significant changes after TIA. RBMS3 was identified as a target gene for miRNA-21a-5p. Downregulation of miRNA-21a-5p expression reduced angiogenesis in animal and cellular models of TIA, and miRNA-21a-5p upregulation had a completely opposite effect. RBMS3 suppression reversed miRNA-21a-5p knockdown-mediated inhibition of angiogenesis in TIA models. Moreover, the TGFBR1/SMAD2/3 pathway was found to be downstream for miRNA-21a-5p/RBMS3.

CONCLUSION

MiRNA-21a-5p conferred neuroprotective effects against TIA by enhancing angiogenesis through the RBMS3/TGFBR1/SMAD2/3 pathway.