The m6A-enriched lncRNA LINC00839 promotes tumor progression by binding TAF15 and activate AOC1 transcription in nasopharyngeal carcinoma [ChIP-Seq]
Dysregulations of long non-coding RNAs (lncRNA) contribute to tumorigenesis by modulating specific cancer-related pathways, but the roles of m6A-enriched lncRNAs and underlying mechanisms remain elusive in nasopharyngeal carcinoma (NPC). Here, we reanalyzed the previous genome-wide analysis of lncRNA profile, and discerned that an oncogenic m6A-enriched lncRNA, LINC00839, which was substantially upregulated in NPC and correlated with poor clinical prognosis, promoted NPC growth and metastasis in vitro and in vivo. Mechanistically, LINC00839 interacted directly with transcription factor, TATA-box binding protein associated factor (TAF15), and coordinated its recruitment to promoter region of amine oxidase copper-containing 1 (AOC1), thereby activating AOC1 transcription in trans. Ectopic expression of AOC1 partially rescued the inhibitory effect of downregulation of LINC00839 in NPC. Furthermore, silencing vir like m6A methyltransferase associated (VIRMA) and insulin-like growth factor 2 mRNA-binding proteins 1 (IGF2BP1) were found to attenuate the expression level and RNA stability of LINC00839 in an m6A-dependent manner. This study unveils a novel oncogenic VIRMA/IGF2BP1–LINC00839–TAF15–AOC1 axis, and highlights significance and prognostic value of LINC00839 in NPC carcinogenesis. Overall design: We reanalyzed the previous genome-wide analysis of lncRNA profile. The in vitro and in vivo functions of LINC00839 were confirmed by CCK8, colony formation, transwell migration and invasion assays, and animal experiments. RNA pulldown, mass spectrometry, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (CHIP) were conducted to investigate the downstream gene modulated by LINC00839. Methylated RIP (MeRIP) and RNA stability assays were performed to clarify the N6-methyladenosine (m6A)-modified status and attenuated rates of LINC00839.