METTL3 promotes colorectal cancer metastasis by promoting the maturation of pri-microRNA-196b.

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.

• Authors: Lanlan Huang, Danlu Liang, Yu Zhang, Xiaoting Chen, Junxiong Chen, Chuangyu Wen, Huanliang Liu, Xiaorong Yang, Xiangling Yang, Shaoqiang Lin
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 149 Issue 8 Pg. 5095-5108 (Jul 2023) ISSN: 1432-1335 [Electronic] Germany
• PMID: 36348020 (Publication Type: Journal Article)
• Copyright: © 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Chemical References

• MicroRNAs
• Adenosine
• Methyltransferases
• METTL3 protein, human

Topics

• Humans
• MicroRNAs (genetics)
• Adenosine
• Cell Movement (genetics)
• Methyltransferases (genetics)
• Colorectal Neoplasms (genetics)