MicroRNA-1 promotes apoptosis of cerebral vascular smooth muscle cells in intracranial aneurysm through targeting Bcl-2

Purpose: The aim of this study was to evaluate whether microRNA-1 (miR-1) facilitates the apoptosis of cerebral vascular smooth muscle cell (VSMC) through inhibiting Bcl-2 in the pathogenesis of intracranial aneurysm (IA). Methods: The rats in control groups (n=12) received no operation and just normal diet, and the rats in aneurysm group (n=12) received operation and normal diet containing 1% normal saline in order to induce IA. Then, the rats were euthanized, their cerebral arteries were dissected for cerebral VSMCs culture, and the regions of aneurysmal dilation on the cerebral arteries were dissected for size measurement and miR-1 expression analysis. Cerebral VSMCs were transfected with different oligonucleotides and then the relationship between miR-1 and Bcl-2 expression in cerebral VSMCs was detected. Luciferase reporter assay was used to investigate the interaction between miR-1 and Bcl-2. Cell proliferation was determined through using CCK-8 assay and colony formation assay. Cell apoptosis was detected through flow cytometry. Results: The expression levels of miR-1 were dramatically up-regulated in the regions of aneurysmal dilation of IA rat models and significantly correlated to the sizes of aneurysms. MiR-1 directly targeted Bcl-2 and down-regulated Bcl-2 expression in cerebral VSMCs. Moreover, we found that inhibition of miR-1 greatly suppressed the proliferation ability and promoted the apoptosis of cerebral VSMCs through regulating Bcl-2 expression. Conclusion: Our results suggested that miR-1 might be a key molecule in regulating cerebral VSMC proliferation and apoptosis through directly down-regulating Bcl-2, revealing that specific modulation of miR-1 in cerebral VSMCs served as an effective approach for the treatment of IA.