LncRNA-MALAT1 promotes tumorogenesis of infantile hemangioma by competitively binding miR-424 to stimulate MEKK3/NF-κB pathway

Abstract Aims Infantile hemangioma (IH) is the most common vascular neoplasm in infant and young children. Long non-coding RNAs (lncRNAs) are known to be associated with IH. This study aims to investigate the role and underlying mechanism of lncRNA-MALAT1 in IH. Main methods qRT-PCR was used to quantify the expressions of MALAT1, miR-424, and MEKK3 in IH tissues. The cell proliferation, apoptosis, migration, invasion, and tube formation ability were assessed by MTT assay, colony formation assay, flow cytometric analysis, transwell assay and tube formation assay, respectively. The interaction among MALAT1, miR-424 and MEKK3 was evaluated by luciferase reporter assay. Immunohistochemistry (IHC) and Western blotting were utilized to evaluate the expression levels of MEKK3, Ki-67 and NF-κB pathway-related proteins both in vitro and in vivo. Key findings In IH tissues, MALAT1 and MEKK3 were overexpressed while miR-424 was down-regulated. Silencing MALAT1 or overexpression of miR-424 significantly inhibited the IH cell proliferation, migration and tube formation, but promoted the cell apoptosis. Knockdown of MALAT1 suppressed the expression of MEKK3 and inactivated the IKK/NF-κB pathway by sponging miR-424. Overexpression of MEKK3 in HemEcs reversed the impact of knockdown of MALAT1 and overexpression of miR-424 on the cell proliferation, apoptosis, migration, invasion and tube formation rate. The tumor xenografts experiments demonstrated that silencing MALAT1 significantly inhibited the tumor growth in vivo and Ki-67 in the tumor tissues was also significantly suppressed. Significance MALAT1 promoted the IH progression through inhibiting miR-424 to activate MEKK3-mediated IKK/NF-κB pathway, suggesting that MALAT1, miR-424 and MEKK3 could be used as potential targets to improve IH treatment efficiency.