ABSTRACT miR‐4458 is linked to cancer, and PRTG, an AS‐related RA pathway gene, is a predicted target. This study clarifies miR‐4458's role in AS and whether it modulates VSMC behaviors via PRTG and the RA pathway. Vascular smooth muscle cells (VSMCs) were treated with oxidized low‐density lipoprotein (ox‐LDL) to establish AS models, and RT‐qPCR was applied to detect expression levels of miR‐4458, PRTG, α‐SMA, SM22α, vimentin, osteopontin, CRABP2, and RARRES1. Cell viability and migration ability were assessed via Cell Counting Kit‐8 (CCK‐8) and Transwell assay. Targeting between miR‐4458 and PRTG was verified via dual‐luciferase reporter gene assay (DLR assay).ox‐LDL treatment upregulated miR‐4458, downregulated PRTG, and enhanced cell viability and migration. miR‐4458 overexpression promoted ox‐LDL‐mediated cell viability and migration, and facilitated VSMC phenotypic transformation. In contrast, miR‐4458 knockdown counteracted the aforementioned ox‐LDL effects. PRTG was confirmed as a target of miR‐4458 via DLR assay, and its knockdown significantly enhanced the stimulatory effect of miR‐4458 knockdown on cell viability and migration. miR‐4458 is highly expressed in AS, which can promote the transformation of smooth muscle cells (SMCs) to smooth muscle cells (SEMs), as well as the proliferation and migration of SMCs, thereby accelerating the progression of AS. Interaction between the miR‐4458/PRTG axis and retinoic acid (RA) signaling pathway could be harnessed therapeutically to modulate VSMC phenotype in ox‐LDL‐induced AS.
Liu et al. (Tue,) studied this question.