2. Academic Validation
  3. METTL3 enhances the stability of MALAT1 with the assistance of HuR via m6A modification and activates NF-κB to promote the malignant progression of IDH-wildtype glioma

METTL3 enhances the stability of MALAT1 with the assistance of HuR via m6A modification and activates NF-κB to promote the malignant progression of IDH-wildtype glioma

  • Cancer Lett. 2021 Jul 28;511:36-46. doi: 10.1016/j.canlet.2021.04.020.
Yu-Zhou Chang 1,  Rui-Chao Chai 2,  Bo Pang 3,  Xin Chang 4,  Song Yuan An 5,  Ke-Nan Zhang 3,  Tao Jiang 6,  Yong-Zhi Wang 7
Affiliations

Affiliations

  • 1 Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
  • 2 Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Chinese Glioma Genome Atlas Network (CGGA), China. Electronic address: [email protected].
  • 3 Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Chinese Glioma Genome Atlas Network (CGGA), China.
  • 4 Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China; Chinese Glioma Genome Atlas Network (CGGA), China.
  • 5 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Chinese Glioma Genome Atlas Network (CGGA), China.
  • 6 Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Chinese Glioma Genome Atlas Network (CGGA), China.
  • 7 Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Chinese Glioma Genome Atlas Network (CGGA), China. Electronic address: [email protected].
PMID: 33933553 DOI: 10.1016/j.canlet.2021.04.020
Abstract

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-κB. 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-κB with a primary focus on m6A modification.

Keywords

Glioma; LncRNA; METTL3; NF-κB; RNA modification.

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