Methyl CpG binding protein 2 promotes colorectal cancer metastasis by regulating N6 -methyladenosine methylation through methyltransferase-like 14.

Abstract

RNA N6 -methyladenosine (m6 A) is an emerging regulatory mechanism for tumor progression in several types of cancer. However, the underlying regulation mechanisms of m6 A methylation in colorectal cancer (CRC) remain unknown. Although the oncogenic function of methyl CpG binding protein 2 (MeCP2) has been reported, it is still unclear whether MeCP2 could alter RNA m6 A methylation state. Here, we systematically identified MeCP2 as a prometastasis gene to regulate m6 A methylation in CRC. Interestingly, MeCP2 could bind to methyltransferase-like 14 (METTL14) to coregulate tumor suppressor Kruppel-like factor 4 (KLF4) expression through changing m6 A methylation modification. Furthermore, insulin-like growth factor 2 mRNA-binding protein 2 recognized the unique modified m6 A methylation sites to enhance KLF4 mRNA stability. Taken together, these findings highlight the novel function of MeCP2 for regulating m6 A methylation and reveal the underlying molecular mechanism for the interaction between MeCP2 and METTL14, which offers a better understanding of CRC progression and metastasis.

• Authors: Shuo Wang, Meifu Gan, Chaoyi Chen, Yi Zhang, Jianlu Kong, Honghe Zhang, Maode Lai
• Journal: Cancer science (Cancer Sci) Vol. 112 Issue 8 Pg. 3243-3254 (Aug 2021) ISSN: 1349-7006 [Electronic] England
• PMID: 34097350 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• KLF4 protein, human
• Klf4 protein, mouse
• Kruppel-Like Factor 4
• Kruppel-Like Transcription Factors
• MECP2 protein, human
• Methyl-CpG-Binding Protein 2
• N-methyladenosine
• METTL14 protein, human
• Methyltransferases
• Adenosine

Topics

• Adenosine (analogs & derivatives, metabolism)
• Animals
• Cell Line, Tumor
• Colorectal Neoplasms (genetics, metabolism)
• Disease Progression
• Gene Expression Regulation, Neoplastic
• HCT116 Cells
• HT29 Cells
• Humans
• Kruppel-Like Factor 4
• Kruppel-Like Transcription Factors (genetics)
• Methyl-CpG-Binding Protein 2 (metabolism)
• Methyltransferases (genetics)
• Mice
• Neoplasm Transplantation
• RNA Stability
• Up-Regulation