Objective: To explore the differential expression of circLRP6 targeted miR-145 in intracranial aneurysms and its regulation of VSMC biological activity, providing a theoretical foundation for the study of intracranial aneurysm regulation by circLRP6.
Methods: Expression levels of circLRP6 and miR-145 mRNA were measured in intracranial aneurysms and superficial temporal arteries. In vitro experiments were conducted using TNF-αstimulated HBVSMCs to evaluate the expression of circLRP6 and miR-145, as well as cell proliferation, apoptosis, migration, and related protein expression.
Results: CircLRP6 was low expressed in intracranial aneurysms, and MiR-145 showed a trend of Overexpression; With the increase of circLRP6 expression in intracranial aneurysms, expression of miR-145 decreased. The correlation coefficient, r, was -0.5139; After TNF- α following stimulation, phenotype of VSMCs changed, expression of circLRP6 in cells decreased, and expression of miR-145 increased; CircLRP was successfully overexpressed or knocked out in VSMCs cells; Overexpression of circLRP6 can inhibit concentration expression of miR-145; VSMCs cells showed an increasing trend with time. Overexpression of circLRP6 can inhibit the proliferation process of VSMCs cells, The proliferation activity of cells was enhanced after circLRP6 knockout, and Overexpression of miR-145 could enhance the proliferation activity of VSMCs; Overexpression of circLRP6 could promote apoptosis process of VSMCs, while knockout of circLRP6 and Overexpression of miR-145 could inhibit apoptosis ability of VSMCs; Overexpression of circLRP6 can inhibit migration ability of VSMCs cells. Overexpression of circLRP6 after knockout and miR-145 can enhance the migration ability of cells; After circLRP6 overexpression in VSMCs, α-SMA, SM22α And expression concentration of Calponin protein increased, IL-1β. The concentration and expression of MMP-2 and MMP-9 protein decreased After knockout of circLRP6 and Overexpression of miR-145, α-SMA, SM22α, And expression concentration of Calponin protein decreased, IL-1β. The expression of MMP-2 and MMP-9 protein increased (P < .05).
Conclusion: CircLRP6 is low expressed in intracranial aneurysms and negatively correlates with miR-145 expression. CircLRP6 may be involved in the development of intracranial aneurysms by influencing VSMC phenotype transformation. CircLRP6 acts as a natural sponge for miR-145, regulating VSMC proliferation, migration, and differentiation and promoting apoptosis, ultimately inhibiting the development of intracranial aneurysms. This study provides a theoretical basis for clinical research on the mechanism of intracranial aneurysms.