DOCK9 antisense RNA2 interacts with LIN28B to stabilize Wnt5a and boosts proliferation and migration of oxidized low densitylipoprotein-induced vascular smooth muscle cells.

Study has suggested that long non-coding RNA DOCK9 antisense RNA2 (LncRNA DOCK9-AS2) may play an important role in atherosclerosis, but the specific role is unclear. In this article, we aim to explore the role and mechanism of DOCK9-AS2 in the proliferation and migration of vascular smooth muscle cells (VSMCs) in atherosclerosis. VSMCs were treated with oxidized low densitylipoprotein (ox-LDL) for 24 h to establish the model of atherosclerosis in vitro. Gain- and loss-of function experiments were conducted. Cell Counting Kit-8 (CCK-8) assay and Ki67 staining were used to evaluate the ability cell proliferation. Transwell assay and immunofluorescence staining of N-Cadherin and E-cadherin were carried out to detect cell migration. RNA immunoprecipitation (RIP) experiment, pull down assay and mRNA stability analysis were used to assess the relationship of DOCK9-AS2, Wnt5a and LIN28B. Western blot analysis was used to measure the protein expression levels. The results showed that DOCK9-AS2 knockdown inhibited the proliferation and migration of ox-LDL-induced VSMCs. Further study on the interaction between DOCK9-AS2, Wnt5a and LIN28B revealed that LIN28B could both directly interact with DOCK9-AS2 and Wnt5a, and DOCK9-AS2 regulated Wnt5a by targeting LIN28B. In addition, Overexpression of Wnt5a partly abolished the inhibitory effects of LIN28B knockdown or DOCK9-AS2 knockdown on cell proliferation and migration induced by in ox-LDL-induced proliferation and migration. In conclusion, the results showed that DOCK9-AS2 promoted the proliferation and migration of vascular smooth muscle cells in atherosclerosis through regulating Wnt5a by targeting LIN28B.