LncRNA SNHG16 accelerates atherosclerosis and promotes ox-LDL-induced VSMC growth via the miRNA-22–3p/HMGB2 axis

Abstract

Long non-coding RNAs (LncRNAs) are essential regulators in the occurrence and development of AS. Here we aim to explore the underlying molecular mechanism of LncRNA SNHG16 in regulating ox-LDL-induced VSMC proliferation, migration and invasion. After constructing AS in vivo and in vitro models, the expressions of SNHG16, miR-22–3p, HMBG2, proliferation- and metastasis-related proteins were determined by qRT-PCR and Western blot assays. Detection of serological lipids, H&E and Masson staining analysis were conducted to evaluate the AS injury in mice. The effects of ox-LDL treatment on VSMCs were examined by CCK-8, wound scratch and Transwell Chamber assays. The targeted relationship was measured by luciferase reporter and RIP assays. The results showed that SNHG16 and high-mobility group box 2 (HMGB2) expressions were increased while miRNA-22–3p expression was decreased in AS mice and ox-LDL-stimulated VSMCs. Functionally, sh-SNHG16 restrained ox-LDL-induced VSMC growth and migration. SNHG16 suppressed miRNA-22–3p expression by direct binding. Furthermore, in ox-LDL-treated VSMCs, miRNA-22–3p mimic prevented proliferation, migration, and invasion. Further explorations showed that HMGB2 was a target of miRNA-22–3p, SNHG16 upregulated HMGB2 levels by acting as a competing endogenous RNA (ceRNA) of miRNA-22–3p. More importantly, sh-HMGB2 partially reversed the effects of sh-SNHG16 together with miR-22–2p inhibitor on ox-LDL-induced VSMC proliferation, migration and invasion. Collectively, SNHG16 accelerated atherosclerotic plaque (AP) formation and enhanced ox-LDL-activated VSMCs proliferation and migration by miRNA-22–3p/HMGB2 axis.