METTL3-stabilized super enhancers-lncRNA SUCLG2-AS1 mediates the formation of a long-range chromatin loop between enhancers and promoters of SOX2 in metastasis and radiosensitivity of nasopharyngeal carcinoma

BackgroundSuper enhancers (SE) play pivotal roles in cell identity and diseases occur including tumorigenesis. The depletion of SE-associated lncRNA transcripts, also known as super-lncRNA, causes the activity of SE to be dysregulated.MethodsWe screened and identified an elevated metastasis-associated SE-lncRNA SUCLG2-AS1 in nasopharyngeal carcinoma (NPC) using RNA-sequencing, real-time quantitative polymerase chain reaction (RT-qPCR) and bioinformatics. Western blotting, RT-qPCR, methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation, chromatin immunoprecipitation, RNA pull-down and 3C (chromosome conformation capture assays) were used for mechanistic studies.ResultsSUCLG2-AS1 was correlated with a poor prognosis. SUCLG2-AS1 promotes NPC cell invasion and metastasis while repressing apoptosis and radiosensitivity in vitro and in vivo. Mechanistically, high SUCLG2-AS1 expression occurred in an m6A-dependent manner. SUCLG2-AS1 was found to be located in the SE region of SOX2, and it regulated the expression of SOX2 via long-range chromatin loop formation, which via mediating CTCF (transcription factor) occupied the SE and promoter region of SOX2, thus regulating the metastasis and radiosensitivity of NPC.ConclusionsTaken together, our data suggest that SUCLG2-AS1 may serve as a novel intervention target for the clinical treatment of NPC. SUCLG2-AS1 was upregulated in nasopharyngeal carcinoma (NPC) tissues and associated with poor prognosis in NPC patients.SUCLG2-AS1 promotes cell invasion and metastasis while repressing apoptosis and radiosensitivity in vitro and in vivo.The writing of SUCLG2-AS1 m6A modified promotes RNA stability of SUCLG2-AS1.Upregulated SUCLG2-AS1 activates expression of SOX2 via long-range chromatin loop formation, which via mediating CTCF occupied super-enhancer and promoter region of SOX2 by SUCLG2-AS1.image