miR-20a-5p/RBM24 Axis Alleviated Hypertensive Intracerebral Hemorrhage via Regulating HIF1α/VEGFA Signaling Pathway

Abstract

Background: Hypertensive intracerebral hemorrhage presented high incidence and high mortality owing to its difficult to diagnose. However, the molecular mechanism of HICH remains unclear. Therefore, this study aims to investigate the key miRNAs and the mechanism of the key miRNAs in HICH. Methods: miRNAs chip was used to explore the differentially expressed miRNAs in HICH patients. In vitro and in vivo HICH models were established by Ang-II. Cell Counting Kit-8 (CCK8), flow cytometry, transwell assay and tube formation analysis were used to detect cell proliferation, apoptosis, cell migration and tube formation, respectively. Hematoxylin-eosin staining was used to evaluate the intracerebral hemorrhage in vivo HICH model. The regulatory mechanism of miR-20a-5p in HICH was confirmed by dual luciferase reporter assay, immunofluorescence, qRT-PCR, western blot and rescue experiments. Results: miR-20a-5p showed the most downregulated in HICH patients compared with healthy individuals and significantly associated with clinicopathological characteristics of HICH. Upregulation of miR-20a-5p promoted cell proliferation, migration and tube formation while inhibited apoptosis in vitro and ameliorated the development of HICH in vivo. RBM24 is a direct target of miR-20a-5p and silencing RBM24 could partially recovery the development of HICH caused by miR-20a-5p inhibition both in vivo and in vitro. miR-20a-5p regulated the development of HICH depending on HIF1α/VEGFA pathway. Conclusion: Our results demonstrated that miR-20a-5p/RBM24 axis regulated hypertensive intracerebral hemorrhage via regulating HIF1α/VEGFA signaling pathway, in support of further investigation into miR-20a-5p therapies for HICH treatment.