m1A methylase TRMT6 promotes neuroblastoma development by demethylating SST mRNA in an m1A/YTHDF2-dependent manner
m1A, a prevalent RNA modification found in various RNA species, was recently reported to modulate cancer progression; However its effects in neuroblastoma have not been investigated. In this study, we observed a significantly elevated expression of m1A transmethylase TRMT6 in high-risk and late-stage neuroblastoma patients. Silence and regain of function studies demonstrated that TRMT6 promotes neuroblastoma cell malignancy, tumor growth, and metastasis in vitro and in vivo. Omics analysis and cancer malignancy assay revealed that somatostatin (SST) is the functional downstream target of TRMT6, which determined the pro-tumor role of TRMT6 in neuroblastoma. Mechanistically, TRMT6 reduces SST mRNA levels by inhibiting its mRNA stability in an m1A-YTHDF2-dependent manner, which revealed the crosstalk of the m1A methylase TRMT6 in neuroblastoma. Moreover, SST analog octreotide suppresses neuroblastoma cell malignancy, tumor growth, and metastasis. Targeting TRMT6 provides a novel potential diagnosis and therapeutic target for neuroblastoma Overall design: Silence TRMT6  to detect the m1A modification variation in SK-N-AS neuroblastoma cells. m1A-seq