YTHDF2: a key RNA reader and antitumor target
Sai Jin Xiao, Songqi Duan, Michael A. Caligiuri, Shoubao Ma, Jianhua Yu
Abstract
N 6 -methyladenosine (m 6 A) is a key mRNA modification influencing mRNA stability and translation. YTHDF2, a major m 6 A ‘reader', was initially recognized for promoting mRNA decay but is now also known to enhance translation by binding to methylated mRNAs. YTHDF2 maintains the function of immune suppressive cells, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs), while also supporting cytotoxic immune cells, including natural killer (NK) and CD8 + T cells. Additionally, YTHDF2 acts as a tumor-intrinsic regulator orchestrating tumor immune evasion. Its multifaceted roles in tumor immunity make YTHDF2 a promising yet challenging therapeutic target. This review explores the complex roles and mechanisms of YTHDF2 in cancers, immune regulation, and tumor immune evasion and highlights emerging therapeutic strategies that target YTHDF2.