Journal
CANCER LETTERS
Volume 511, Issue -, Pages 36-46Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2021.04.020
Keywords
Glioma; RNA modification; METTL3; LncRNA; NF-kappa B
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Funding
- National Natural Science Foundationof China [81773208, 81903078]
- National Key Research and Development Program of China [2019YFE0108100]
- Beijing Nova Program [Z201100006820118]
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The study confirmed the role of METTL3 in IDH-wildtype gliomas, promoting malignant progression by enhancing the stability of MALAT1.
Understanding the role of N6-methyladenosine (m6A) in tumorigenesis and stem cell maintenance is an emerging field in glioma research. However, it is necessary to study the function of m6A in IDH-mutation and IDH-wildtype gliomas separately. Here, we aimed to elucidate the role and mechanism of the m6A writer METTL3 in regulating the malignant progression of IDH-wildtype gliomas. We demonstrated that METTL3 expression is positively associated with a higher malignant grade and poorer prognosis of IDH-wildtype gliomas but not IDH-mutant gliomas. METTL3 could also promote the malignant progression of gliomas in both in vitro and in vivo models. Mechanistically, METTL3 upregulated MALAT1 expression by enhancing its stability via m6A modification. We further revealed that HuR was essential for METTL3-mediated MALAT1 stabilization, and upregulated MALAT1 subsequently activated NF-kappa B. Taken together, our findings confirmed that METTL3 promoted the malignant progression of IDH-wildtype gliomas and revealed important insight into the upstream regulatory mechanism of MALAT1 and NF-kappa B with a primary focus on m6A modification.
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