m6A reader YTHDF1 inhibits the growth of neuroblastoma in vitro and in vivo

Abstract

Abstract Purpose Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, always leading to an unfavorable prognosis. m6A is the most prevalent modification in eukaryotic RNAs. Util now, the role of N6-methyladenosine (m6A) in NB has not been elucidated. In this study, we aim to explore the role of m6A reader YTHDF1 in regulating NB proliferation and growth in vitro and in vivo.Methods We evaluate the role of YTHDF1 in mediating NB cell growth using in vitro and in vivo methods. We perform immunohistochemistry assay to detect the expression of YTHDF1 in NB clinical samples. Cell proliferation assay was used to test the growth of NB cell line. The tumor xenograft mouse model was performed to evaluate the role of YTHDF1 in vivo. RNA-seq was applied to uncover the genes that changed upon YTHDF1 knockdown.Results Our results showed that the expression of YTHDF1 is significantly increased in clinical neuroblastoma samples compared with that of ganglioneuroma (GN) and ganglioneuroblastoma (GNB). Cellular assays demonstrated that knockdown of YTHDF1 inhibits NB cell growth and proliferation. The tumor xenograft mouse model suggests that knockdown of YTHDF1 suppresses the growth of neuroblastoma in vivo. RNA-seq showed that the expression of a series genes was changed upon YTHDF1 knockdown, including ACER3, WNT2B and ANKRD62.Conclusion In conclusion, our study provides a new therapeutic target for the treatment of neuroblastoma via inhibiting YTHDF1.