LINC01956 promotes metastasis and M2 polarization of tumor-associated macrophages in glioblastoma via the FUS/β-catenin signaling pathway

Abstract Long noncoding RNAs (lncRNAs) can drive cancer progression. Here, we studied the role of a novel lncRNA, LINC01956, in glioblastoma (GBM). The level of LINC01956 was elevated in GBM cell lines and tissues. LINC01956 downregulation suppressed the migration and proliferation of GBM cells both in vitro and in vivo. Silencing of LINC01956 also significantly suppressed the growth of patient-derived organoids. 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. Taken together, our data revealed for the first time that LINC01956 exerts pro-tumor effects via FUS-dependent activation of the WNT/β-catenin signaling pathway.