glucuronyl-glucosamine-glycan-sulfate and Glioma

The prognosis for diffuse gliomas is very poor and the mechanism underlying their malignant progression remains unclear. Here, we aimed to elucidate the role and mechanism of the RNA N6,2'-O-dimethyladenosine (m. YTHDF2 mRNA levels and functions were assessed using several independent datasets. Western blotting, quantitative polymerase chain reaction, and immunohistochemistry were used to evaluate the expression levels of YTHDF2 and other molecules in human and mouse tumor tissues and cells. Knockdown and overexpression were used to evaluate the effects of YTHDF2, methyltransferase-like 3 (METTL3), and UBX domain protein 1 (UBXN1) on glioma malignancy in cell and orthotopic xenograft models. RNA immunoprecipitation (RIP), methylated RIP, and RNA stability experiments were performed to study the mechanisms underlying the oncogenic role of YTHDF2.. YTHDF2 expression was positively associated with a higher malignant grade and molecular subtype of glioma and poorer prognosis. YTHDF2 promoted the malignant progression of gliomas in both in vitro and in vivo models. Mechanistically, YTHDF2 accelerated UBXN1 mRNA degradation via METTL3-mediated m. Our findings confirmed that YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-κB activation via UBXN1 with a primary focus on m

Topics: Adaptor Proteins, Signal Transducing; Adenosine; Animals; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Glioma; Humans; Methyltransferases; Mice, Inbred BALB C; Mice, Nude; NF-kappa B; RNA Stability; RNA-Binding Proteins; RNA, Messenger