Dynamic Expression of m6A Regulators During Multiple Human Tissue Development and Cancers

Abstract

N6-methyladenosine (m⁶A) plays critical roles in human development and cancer progression. However, our knowledge regarding the dynamic expression of m⁶A regulators during human tissue development is still lacking. Here, we comprehensively analyzed the dynamic expression alterations of m⁶A regulators during seven tissue development and eight cancer types. We found that m⁶A regulators globally exhibited decreased expression during development. In addition, IGF2BP1/2/3 (insulinlike growth factor 2 MRNA-binding protein 1/2/3) exhibited reverse expression pattern in cancer progression, suggesting an oncofetal reprogramming in cancer. The expressions of IGF2BP1/2/3 were regulated by genome alterations, particularly copy number amplification in cancer. Clinical association analysis revealed that higher expressions of IGF2BP1/2/3 were associated with worse survival of cancer patients. Finally, we found that genes significantly correlated with IGF2BP1/2/3 were significantly enriched in cancer hallmark-related pathways. In summary, dynamic expression analysis will guide both mechanistic and therapeutic roles of m⁶A regulators during tissue development and cancer progression.