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

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RNA N6‐methyladenosine (m6A) is an emerging regulatory mechanism for tumor progression in several types of cancer. However, the underlying regulation mechanisms of m6A 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 m6A methylation state. Here, we systematically identified MeCP2 as a prometastasis gene to regulate m6A methylation in CRC. Interestingly, MeCP2 could bind to methyltransferase‐like 14 (METTL14) to coregulate tumor suppressor Kruppel‐like factor 4 (KLF4) expression through changing m6A methylation modification. Furthermore, insulin‐like growth factor 2 mRNA‐binding protein 2 recognized the unique modified m6A methylation sites to enhance KLF4 mRNA stability. Taken together, these findings highlight the novel function of MeCP2 for regulating m6A methylation and reveal the underlying molecular mechanism for the interaction between MeCP2 and METTL14, which offers a better understanding of CRC progression and metastasis.