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

Background: Super 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.

Methods: We 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.

Results: SUCLG2-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.

Conclusions: Taken together, our data suggest that SUCLG2-AS1 may serve as a novel intervention target for the clinical treatment of NPC.

SOX2; SUCLG2-AS1; nasopharyngeal carcinoma; radiosensitivity; super-enhancer.