In:
Oncogene, Springer Science and Business Media LLC, Vol. 40, No. 39 ( 2021-09-30), p. 5814-5828
Kurzfassung:
5-Methylcytosine (m 5 C) is a posttranscriptional RNA modification participating in many critical bioprocesses, but its functions in human cancer remain unclear. Here, by detecting the transcriptome-wide m 5 C profiling in esophageal squamous cell carcinoma (ESCC), we showed increased m 5 C methylation in ESCC tumors due to the overexpressed m 5 C methyltransferase NSUN2. Aberrant expression of NSUN2 was positively regulated by E2F Transcription Factor 1 (E2F1). High NSUN2 levels predicted poor survival of ESCC patients. Moreover, silencing NSUN2 suppressed ESCC tumorigenesis and progression in Nsun2 knockout mouse models. Mechanistically, NSUN2 induced m 5 C modification of growth factor receptor-bound protein 2 ( GRB2 ) and stabilized its mRNA, which was mediated by a novel m 5 C mediator, protein lin-28 homolog B (LIN28B). Elevated GRB2 levels increased the activation of PI3K/AKT and ERK/MAPK signalling. These results demonstrate that NSUN2 enhances the initiation and progression of ESCC via m 5 C-LIN28B dependent stabilization of GRB2 transcript, providing a promising epitranscriptomic-targeted therapeutic strategy for ESCC.
Materialart:
Online-Ressource
ISSN:
0950-9232
,
1476-5594
DOI:
10.1038/s41388-021-01978-0
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2021
ZDB Id:
2008404-3
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