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

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.