METTL3 Promotes Colorectal Cancer Metastasis by Promoting the Maturation of Pri-microRNA-196b

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2022 Nov 8

PMID 36348020

Authors

Lanlan Huang

Danlu Liang

Yu Zhang

Xiaoting Chen

Junxiong Chen

Chuangyu Wen

Huanliang Liu

Xiaorong Yang

Xiangling Yang

Shaoqiang Lin

Affiliations

Soon will be listed here.

Abstract

Purpose: Methyltransferase-like 3 (METTL3), a key member of the m6A methyltransferase complex, is upregulated in multiple human malignancies and plays a role in regulating tumor migration. This study aimed to reveal the underlying mechanism by which METTL3 in regulates the metastasis of colorectal cancer (CRC).

Methods: We compared METTL3 expression levels in CRC tumor tissues and adjacent nontumor tissues by immunohistochemistry (IHC). The functional roles of METTL3 in CRC were assessed by real-time cell migration assays, wound-healing assays and Transwell assays. miRNA sequencing (miRNA-seq), RNA-binding protein immunoprecipitation (RIP) assays and N6-methyladenosine immunoprecipitation (MeRIP) assays were performed to confirm the molecular mechanism underlying the involvement of METTL3 in CRC cell metastasis.

Results: We found that METTL3 was overexpressed in CRC tissues. METTL3 knockdown significantly inhibited CRC cell migration and invasion, while METTL3 overexpression had the opposite effects. Furthermore, we demonstrated that METTL3 regulates miR-196b expression via an N6-methyladenosine (m6A)-pri-miR-196b-dependent mechanism and thereby promotes CRC metastasis.

Conclusion: This study shows the important role of METTL3 in CRC metastasis and provides novel insight into m6A modification in CRC metastasis.

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