LncRNA MALAT1 modulates ox-LDL induced EndMT through the Wnt/-catenin signaling pathway

BackgroundEndothelial-to-mesenchymal transition (EndMT) plays significant roles in atherosclerosis, but the regulatory mechanisms involving lncRNAs remain to be elucidated. Here we sort to identify the role of metastasis-associated lung adenocarcinoma transcript1 (MALAT1) in ox-LDL-induced EndMT.MethodsThe atherosclerosis model was established by feeding ApoE(-/-) mice with high-fat diet, and the levels of lncRNA MALAT1 in mouse arterial tissue were detected by RT-qPCR. Cell model was established by treating human umbilical vein endothelial cells (HUVECs) with ox-LDL, and the levels of EndMT markers, such as CD31, vWF, -SMA and Vimentin and lncRNA MALAT1 levels were detected and their correlations were analyzed. The role of MALAT1 in EndMT and its dependence on Wnt/-catenin signaling pathway was further detected by knocking down or overexpressing MALAT1.ResultsMALAT1 was upregulated in high-fat food fed ApoE(-/-) mice. HUVECs treated with ox-LDL showed a significant decrease in expression of CD31 and vWF, a significant increase in expression of -SMA and vimentin, and upregulated MALAT1. An increased MALAT1 level facilitated the nuclear translocation of -catenin induced by ox-LDL. Inhibition of MALAT1 expression reversed nuclear translocation of -catenin and EndMT. Moreover, overexpression of MALAT1 enhanced the effects of ox-LDL on HUVEC EndMT and Wnt/-catenin signaling activation.ConclusionsOur study revealed that the pathological EndMT required the activation of the MALAT1-dependent Wnt/-catenin signaling pathway, which may be important for the onset of atherosclerosis.Trial registrationNot applicable.