| HRA002365
(Open Access)
|
Here, we show that circular MET RNA (circMET) encodes a 404 amino acid novel MET variant (MET404) facilitated by the N6 methyladenosine (m6A) reader YTHDF2. Genetic ablation of circMET inhibited MET404 expression in mice and attenuated MET signalling. Conversely, MET404 knock-in plus P53 knock-out in mouse astrocytes initiated glioblastoma tumorigenesis and shortened overall survival. MET404 directly interacts with the MET beta subunit and forms a constitutively activated MET receptor whose activity does not require HGF stimulation. High MET404 expression predicts poor prognosis in glioblastoma patients, indicating its clinical relevance. Targeting MET404 through a neutralizing antibody or genetic ablation reduced glioblastoma tumorigenicity in vitro and in vivo. These are the m6A sequencing data of 10 GBM samples. |
