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. 2022 Nov 6;17(2):195–229. doi: 10.1002/1878-0261.13326

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© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Fig. 5 — Mechanism of m⁶A on cancer metastasis. m⁶A modulates metastasis via various mechanisms in cancers. (A) METTL3 deposits m⁶A on CDS of Snail mRNA and then targeted by YTHDF1 to increase its translation to mediate metastasis in liver cancer [101]. (B) FTO‐mediated demethylation of m⁶A on CLIC4 mRNA decreases its stability, resulting in the repression of metastasis in PRAD cells [210]. (C) IGF2BP3 helps stabilize the mRNA stability of PKMYT1 via an ALKBH5‐dependent manner to regulate metastasis in GC cells [211]. (D) IGF2BP2 recognize m⁶A on IGF1R mRNA and increase its expression to activate RhoA‐ROCK pathway and therefore promote metastasis in GC cells [212]. (E) YTHDF3 promotes metastasis by inducing the translation of ST6GALNAC5, GJA1, EGFR and VEGFA mRNAs in BC cells [60]. (F) METTL3 promotes metastasis by methylating lncRNA PCAT6, which recognized by IGF2BP2 to stabilize IGF2BP2/IGF1R interaction in PRAD cells [73]. (G) m⁶A‐modificed lncRNA RP11 forms complex with hnRNPA2B1, accelerating the mRNA degradation of Siah1 and Fbxo45 to mediate metastasis by targeting of Zeb1 in CRC cells [141]. (H) m⁶A‐modificed miR‐143‐3p binds to the 3′UTR of VASH1 to promote metastasis in LC cells [127]. (I) YTHDC1 recognizes m⁶A‐modified circNSUN2 to enhance the circNSUN2/ HMGA2/IGF2BP2 interaction to promote metastasis in CRC cells [213]. (J) ALKBH5‐mediated demethylation of circCPSF6 promotes metastasis by activating YAP1 in HCC cells [214].