NCYM facilitates cell proliferation and invasion in Wilms tumor by regulating SIX1/β-catenin axis

Recently, accumulating studies demonstrate that some long non-coding RNAs (lncRNAs) contain open read frames and have protein/peptide-coding potential. NCYM is a 109-amino acid product encoded by lncRNA MYCNOS variant 2 that is an antisense transcript of MYCN oncogene. NCYM is amplified in human neuroblastomas and associated with poor prognosis. However, its functional role in Wilms tumor (WT) remains unclear. In this study, we identified lncRNA MYCNOS as a promising prognostic factor in Wilms tumor through bioinformatics analysis. The expression of NCYM and downstream genes was determined by western blotting. Cell proliferation, migration, and invasion were measured by CCK-8, wound healing and Transwell assays, respectively. Cell apoptosis was evaluated by flow cytometry assay. The subcutaneous xenograft and lung metastasis mouse model were established by the armpit injection or tail intravenous injection of WT cells, respectively. Our results showed that NCYM was validated to be abundantly expressed in Wilms tumor cell lines and tissues. The exogenous overexpression of NCYM promoted WT cell proliferation, migration, and invasion. The silencing of SIX1 expression abolished the pro-growth effect of NCYM and downregulated β-catenin in WT. Additionally, NCYM facilitated tumor growth and formation of lung metastasis in vivo. In summary, the exogenous overexpression of NCYM could play a critical role in WT progression by mediating SIX1 and β-catenin as an oncopromoting factor.