A functional polymorphism in the promoter region of miR-155 predicts the risk of intracranial hemorrhage caused by rupture intracranial aneurysm.

BACKGROUND

This study aimed to study the effect and underlying molecular mechanisms of single-nucleotide polymorphism (SNP) rs767649 during the pathogenesis of intracranial aneurysm (IA) rupture.

METHOD

Real-time PCR and Western blot analysis were performed to detect the differentiated expression of miR-155 and matrix metalloproteinase-2 (MMP-2) among different sample groups. Computational analysis and luciferase assay were conducted to study the effect of SNP rs767649 on the expression of miR-155 as well as the regulatory relationship between miR-155 and MMP-2.

RESULTS

In unruptured IA samples, the expression of miR-155 was upregulated while the expression of MMP-2 was downregulated compared with the ruptured IA samples. Similarly, the expression of miR-155 was upregulated while the expression of MMP-2 was downregulated in samples genotyped as AA/AT compared with samples genotyped as TT. In addition, compared with the negative controls, the luciferase activities of cells treated with rs767649A and rs767649T were both elevated with rs767649A-transfected cells expressing the highest luciferase activity. Furthermore, a negative relationship was established between miR-155 and MMP-2 by measuring the luciferase activity of cells cotransfected with miR-155 and the wild-type 3'-untranslated region of MMP-2.

CONCLUSION

The results of this study showed that the SNP rs767649 in the promoter of miR-155 could reduce the transcription activity of miR-155, while poorly expressed miR-155 could increase the incidence of IA rupture by increasing the expression of MMP-2, especially in subjects carrying the TT genotype of SNP rs767649.