Roles of METTL3 in cancer: mechanisms and therapeutic targeting

Chengwu Zeng; Wanxu Huang; Yangqiu Li; Hengyou Weng

doi:10.1186/s13045-020-00951-w

Roles of METTL3 in cancer: mechanisms and therapeutic targeting

J Hematol Oncol. 2020 Aug 27;13(1):117. doi: 10.1186/s13045-020-00951-w.

Authors

Chengwu Zeng^{1

2}, Wanxu Huang^{1

3}, Yangqiu Li⁴, Hengyou Weng^{5

6}

Affiliations

¹ Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, 510005, China.
² Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China.
³ The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, China.
⁴ Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China. yangqiuli@hotmail.com.
⁵ Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, 510005, China. weng_hengyou@grmh-gdl.cn.
⁶ Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China. weng_hengyou@grmh-gdl.cn.

Abstract

N⁶-methyladenosine (m⁶A) is the most abundant mRNA modification and is catalyzed by the methyltransferase complex, in which methyltransferase-like 3 (METTL3) is the sole catalytic subunit. Accumulating evidence in recent years reveals that METTL3 plays key roles in a variety of cancer types, either dependent or independent on its m⁶A RNA methyltransferase activity. While the roles of m⁶A modifications in cancer have been extensively reviewed elsewhere, the critical functions of METTL3 in various types of cancer, as well as the potential targeting of METTL3 as cancer treatment, have not yet been highlighted. Here we summarize our current understanding both on the oncogenic and tumor-suppressive functions of METTL3, as well as the underlying molecular mechanisms. The well-documented protein structure of the METTL3/METTL14 heterodimer provides the basis for potential therapeutic targeting, which is also discussed in this review.

Keywords: Cancer; Drug discovery; METTL3; Non-coding RNA; RNA modification; m6A.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Adenosine / analogs & derivatives*
Adenosine / metabolism
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Binding, Competitive
Carcinogens
Drug Design
Drug Screening Assays, Antitumor
Gene Expression Regulation, Neoplastic
Humans
Methylation
Methyltransferases / antagonists & inhibitors
Methyltransferases / chemistry
Methyltransferases / genetics
Methyltransferases / physiology*
Models, Molecular
Molecular Targeted Therapy*
Neoplasm Proteins / antagonists & inhibitors
Neoplasm Proteins / chemistry
Neoplasm Proteins / genetics
Neoplasm Proteins / physiology*
Neoplasms / genetics
Neoplasms / metabolism*
Neoplasms / therapy
Oncogenes
Protein Conformation
Protein Domains
RNA Processing, Post-Transcriptional*
RNA, Neoplasm / metabolism*
Recombinant Fusion Proteins / pharmacology
Recombinant Fusion Proteins / therapeutic use
Substrate Specificity
Tumor Suppressor Proteins / antagonists & inhibitors
Tumor Suppressor Proteins / chemistry
Tumor Suppressor Proteins / genetics
Tumor Suppressor Proteins / physiology

Substances

Antineoplastic Agents
Carcinogens
Neoplasm Proteins
RNA, Neoplasm
Recombinant Fusion Proteins
Tumor Suppressor Proteins
N-methyladenosine
Methyltransferases
METTL3 protein, human
Adenosine