Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers

Wenhui Zheng; Xiaoshen Dong; Yan Zhao; Shuo Wang; Haiyang Jiang; Mingdi Zhang; Xinyu Zheng; Ming Gu

doi:10.3389/fonc.2019.01403

Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers

Front Oncol. 2019 Dec 12:9:1403. doi: 10.3389/fonc.2019.01403. eCollection 2019.

Authors

Wenhui Zheng¹, Xiaoshen Dong², Yan Zhao², Shuo Wang², Haiyang Jiang², Mingdi Zhang³, Xinyu Zheng^{2

4}, Ming Gu²

Affiliations

¹ Department of Anesthesiology, The Shengjing Hospital of China Medical University, Shenyang, China.
² Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
³ Department of Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
⁴ Lab 1, Cancer Institute, The First Affiliated Hospital of China Medical University, Shenyang, China.

Abstract

Methyltransferase-like 3 (METTL3), a predominantly catalytic enzyme in the N⁶-methyladenosine (m⁶A) methyltransferase system, is dysregulated and plays a dual role (oncogene or tumor suppressor) in different human cancers. The expression and pro- or anticancer role of METTL3 in different cancers remain controversial. METTL3 is implicated in many aspects of tumor progression, including tumorigenesis, proliferation, invasion, migration, cell cycle, differentiation, and viability. Most underlying mechanisms involve multiple signaling pathways that rely on m⁶A-dependent modification. However, METTL3 can also modulate the cancer process by directly promoting the translation of oncogenes via interaction with the translation initiation machinery through recruitment of eukaryotic translation initiation factor 3 subunit h (eIF3h). In this review, we summarized the current evidence on METTL3 in diverse human malignancies and its potential as a prognostic/ therapeutic target.

Keywords: METTL3; cancer; m6A; mechanism; pathway.

Publication types

Review