miR-4735-3p regulates phenotypic modulation of vascular smooth muscle cells by targeting HIF-1-mediated autophagy in intracranial aneurysm.

Intracranial aneurysm (IA) is recognized as a lethal form of cerebrovascular disease mainly featured with a modulated phenotype of vascular smooth muscle cells (SMCs). It is generally believed that enhanced SMC proliferation and migration capabilities are the main characteristics in this process. In this study, we revealed that microRNA-4735 (miR-4735) participates in phenotypic modulation in a hypoxia-inducible factor-1 (HIF-1)-dependent manner of SMCs. miR-4735 targets the 3'-untranslated region of HIF-1. The downregulated expression of miR-4735 in IA tissues leads to elevated expression of HIF-1, which activates autophagy and promotes autophagy-mediated SMC proliferation and migration. Overexpression of miR-4735 suppressed HIF-1 expression and HIF-1-mediated autophagy, which led to impaired SMC proliferation and migration abilities. Forced expression of HIF-1 in miR-4735-overexpressed SMCs rescued the impaired SMC proliferation and migration abilities. In conclusion, miR-4735 plays an important role in phenotypic modulation in IA by regulating autophagy-promoted SMC proliferation and migration.