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

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Abstract

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.

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Authors and Affiliations

  1. Department of Neurosurgery, First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, China

    Yangchun Hu, Weiwei Chen, Chao Li, Xiaojian Wang, Jing Luo & Baochun Cheng

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  1. Yangchun Hu
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  2. Weiwei Chen
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  3. Chao Li
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  4. Xiaojian Wang
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  5. Jing Luo
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  6. Baochun Cheng
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Contributions

Yangchun Hu designed, supervised the research, and participated in the reviewing of the manuscript. Weiwei Chen guaranteed the integrity of the entire study and participated in writing the manuscript. Chao Li performed the literature research. Xiaojian Wang, Jing Luo and Baochun Cheng performed the experimental studies, data analysis, and statistical analysis. All authors read and approved the final manuscript.

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Correspondence to Yangchun Hu.

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Research protocol was approved by the First Affiliated Hospital of Anhui Medical University. Written informed consent was obtained from all participants.

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Hu, Y., Chen, W., Li, C. et al. LncRNA ANRIL Facilitates Vascular Smooth Muscle Cell Proliferation and Suppresses Apoptosis via Modulation of miR-7/FGF2 Pathway in Intracranial Aneurysms. Neurocrit Care 36, 106–115 (2022). https://doi.org/10.1007/s12028-021-01262-9

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  • DOI: https://doi.org/10.1007/s12028-021-01262-9

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