Downregulation of YTHDF1 inhibits the growth and proliferation of neuroblastoma cells

Neuroblastoma (NB) is an embryonic tumor that is derived from the sympathetic nervous ystem and is associated with an unfavorable prognosis. It is also the most common extracranial solid tumor in children <2 years old. Although there are intensive studies about the tumorigenesis and mechanism of this type of tumor, effective therapeutic targets for it are still lacking. N6-methyladenosine (m6A) is the most prevalent modification of eukaryotic RNAs. To the best of our knowledge, until now, the role of m6A in NB malignance has not been investigated. Thus, the present study aimed to explore the role of the m6A reader YTH N6-methyladenosine RNA binding protein F1 (YTHDF1) in regulating NB proliferation and growth, and the role of YTHDF1 in mediating NB cell growth was evaluated using in vitro and in vivo methods. An immunohistochemistry assay was performed to detect YTHDF1 expression in clinical NB samples. A tumor xenograft mouse model was used to evaluate the role of YTHDF1 in vivo. RNA-sequencing (RNA-seq) was performed to identify the genes with altered expression levels following YTHDF1 downregulation. The results demonstrated that YTHDF1 expression was markedly increased in clinical NB tissues compared with ganglioneuroma and ganglioneuroblastoma tissues. Cellular assays demonstrated that knockdown of YTHDF1 inhibited NB cell growth and proliferation. The experiments using a tumor xenograft mouse model suggested that inhibition of YTHDF1 suppressed the growth of NB in vivo.