Intracranial Aneurysm

ANRIL[LncRNA]

miR-7[miRNA]

FGF2[mRNA]

Vascular Smooth Muscle Cells

Homo sapiens (human)

Neurocrit Care. 2021 Jul 20. doi: 10.1007/s12028-021-01262-9.

LncRNA ANRIL Facilitates Vascular Smooth Muscle Cell Proliferation and Suppresses Apoptosis via Modulation of miR-7/FGF2 Pathway in Intracranial Aneurysms.

RNA immunoprecipitation;Western blot;Luciferase reporter assay;RNA immunoprecipitation;

BACKGROUND: Proliferation and apoptosis of vascular smooth muscle cells (VSMCs) are linked to intracranial aneurysm (IA) formation and progression. Long antisense noncoding RNA in the INK4 locus (ANRIL) has been reported to regulate VSMC functions in several cardiovascular diseases. However, little is known about how ANRIL influences VSMC proliferation and apoptosis during IA pathogenesis. METHODS: The expression level of ANRIL in the plasma and arterial wall tissues of patients with IA was detected by real-time quantitative polymerase chain reaction. The functional role of ANRIL in the regulation of VSMC proliferation and apoptosis and its downstream regulatory mechanism were determined using Cell Counting Kit 8, immunofluorescence, terminal-deoxynucleotidyl transferase-mediated UTP nick end labeling, western blotting, luciferase reporter assay, and RNA immunoprecipitation assay. RESULTS: ANRIL was downregulated in the plasma and arterial wall tissues of patients with IA, when compared with control groups. Overexpression of ANRIL significantly promoted VSMC proliferation and blocked cell apoptosis. Mechanistic studies demonstrated that ANRIL directly bound to microRNA-7 (miR-7) and that overexpression of miR-7 overturned the increased cell proliferation and decreased cell apoptosis, which was induced by ANRIL restoration. Besides, further study showed that ANRIL positively regulated fibroblast growth factor 2 (FGF2) expression via targeting miR-7. CONCLUSIONS: These results suggested that ANRIL affects VSMC proliferation and apoptosis via regulation of the miR-7/FGF2 pathway in IA, which provided a potential novel strategy for the treatment of IA.