METTL3 promotes colorectal cancer metastasis by stabilizing PLAU mRNA in an m6A-dependent manner

Biochem Biophys Res Commun. 2022 Jul 23:614:9-16. doi: 10.1016/j.bbrc.2022.04.141. Epub 2022 May 6.

Abstract

Colorectal cancer (CRC) is one of the most common tumors and ranks second in tumor mortality. N6-methyladenosine (m6A) modification is the most prevalent RNA modification in eukaryotes. As the critical m6A methyltransferase, the role of METTL3 in the metastasis regulation of CRC might be controversial and need to be further explored. In this study, we confirmed that METTL3 could promoted CRC metastasis in vitro and in vivo. METTL3 was upregulated in CRC tissues and led to poor survival in CRC metastasis. We found METTL3 upregulated PLAU mRNA in an m6A-dependent manner, and then participated in MAPK/ERK pathway to promote angiogenesis and metastasis in CRC. Our study provided new therapeutic targets in CRC metastasis treatment.

Keywords: Colorectal cancer; METTL3; Metastasis; PLAU; m6A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism
  • Cell Line, Tumor
  • Colorectal Neoplasms* / pathology
  • Humans
  • Membrane Proteins / genetics*
  • Methyltransferases / metabolism*
  • RNA, Messenger / metabolism*

Substances

  • Membrane Proteins
  • PLAU protein, human
  • RNA, Messenger
  • Methyltransferases
  • METTL3 protein, human
  • Adenosine