LINC01956 Promotes Metastasis and M2 Polarization of Tumor-Associated Macrophages in Glioblastoma Via The FUS/β-Catenin Signaling Pathway
Abstract Background:Long noncoding RNAs (lncRNAs) can drive cancer progression. Here, we studied the role of a novel lncRNA, LINC01956, in glioblastoma (GBM). Methods:RT-PCR assay was used to examine LINC01956 expression levels. Colony-formation, MTT, cell-cycle and in-vivo tumorigenesis assays were used to examine the role of LINC01956 in cell growth in vitro and in vivo. Boyden assay was used to examine cell invasion ability in vitro. RNA immunoprecipitation and RNA-protein pull-down assays were used to examine the interaction between LINC01956 and FUS protein.ChIP assay was used to examine HIF1-binding sites in the LINC01956 promoter.Results:The level of LINC01956 was elevated in GBM cell lines and tissues. LINC01956 downregulation suppressed the migration and proliferation of GBM cells. M2 polarization of macrophages induced by exosomes derived from glioma cells overexpressing LINC01956 further accelerated GBM progression. Mechanistically, we found that FUS interacted with both LINC01956 and β-catenin. LINC01956 bound to FUS and reduced its ubiquitination. LINC01956 evoked nuclear translocation of phosphorylated (p)-β-catenin by recruiting FUS. Furthermore, under hypoxic conditions, LINC01956 was regulated by HIF-1α. Conclusion:Taken together, our data revealed for the first time that LINC01956 exerts protumor effects via FUS-dependent activation of the WNT/β-catenin signaling pathway.