A novel MYCN-YTHDF1 cascade contributes to retinoblastoma tumor growth by eliciting m6A -dependent activation of multiple oncogenes.
Sci China Life Sci
; 66(9): 2138-2151, 2023 09.
Article
en En
| MEDLINE
| ID: mdl-36949231
ABSTRACT
Retinoblastoma, the most prevalent primary intraocular tumor in children, leads to vision impairment, disability and even death. In addition to RB1 inactivation, MYCN activation has been documented as another common oncogenic alteration in retinoblastoma and represents one of the high-risk molecular subtypes of retinoblastoma. However, how MYCN contributes to the progression of retinoblastoma is still incompletely understood. Here, we report that MYCN upregulates YTHDF1, which encodes one of the reader proteins for N6-methyladenosine (m6A) RNA modification, in retinoblastoma. We further found that this MYCN-upregulated m6A reader functions to promote retinoblastoma cell proliferation and tumor growth in an m6A binding-dependent manner. Mechanistically, YTHDF1 promotes the expression of multiple oncogenes by binding to their mRNAs and enhancing mRNA stability and translation in retinoblastoma cells. Taken together, our findings reveal a novel MYCN-YTHDF1 regulatory cascade in controlling retinoblastoma cell proliferation and tumor growth, pinpointing an unprecedented mechanism for MYCN amplification and/or activation to promote retinoblastoma progression.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Retinoblastoma
/
Neoplasias de la Retina
Límite:
Child
/
Humans
Idioma:
En
Revista:
Sci China Life Sci
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China