Background N6-methyladenosine (m6A) is a prevalent RNA modification in eukaryotes that regulates RNA stability and translation. Dysregulated m6A modification is implicated in cancer progression. This study investigated the role of the m6A reader protein, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2 BP2), in the progression of thyroid cancer (TC). Methods Cell proliferation was assessed using cell counting kit-8 (CCK8) and 5-ethynyl-2’-deoxyuridine (EdU) assays. Cell migration and invasion were evaluated by Transwell assays. A xenograft tumor model was employed to examine the impact of IGF2 BP2 on tumor growth in vivo . Gene functional annotation was performed through GO analysis. Spearman correlation analysis was utilized to evaluate the relationship between the expression levels of cathepsin H (CTSH) and IGF2 BP2. RIP-qPCR and RNA pull-down assays were conducted to confirm the interaction between IGF2 BP2 and CTSH mRNA. Results Elevated IGF2 BP2 expression correlated significantly with advanced N stage in TC. Knockdown of IGF2 BP2 inhibited TC cell proliferation, migration, and invasion in vitro , as well as tumor growth in vivo . CTSH expression mirrored IGF2 BP2 expression. IGF2 BP2 interacted with CTSH mRNA, enhancing its stability in an m6A-dependent manner. Overexpression of CTSH counteracted the effects of IGF2 BP2 knockdown on TC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT). Conclusion IGF2 BP2 accelerates TC progression by recognizing and stabilizing m6A-modified CTSH mRNA. IGF2 BP2 and CTSH represent potential diagnostic and therapeutic targets for TC.
Dong et al. (2025) studied this question.