IGF2BP2 (Insulin Like Growth Factor 2 MRNA Binding Protein 2)

Clinically, ROLLCSC and its targets are associated with distinct tumor expression patterns and have prognostic significance. Overall, our study elucidates how the lncRNA ROLLCSC derived from cancer stem cell (CSC)-derived EVs is efficiently transported to LUAD cells, subsequently reshaping the lipid metabolism of recipient cells and enhancing their resistance to ferroptosis.

While this sulfonamide-based inhibitor exhibits clear biochemical activity and a defined binding mode at the KH34 RNA-binding interface, its limited cellular permeability and high plasma protein binding currently preclude cellular efficacy. This work identifies a new structural class of IMP2 KH34 inhibitors serving as a starting point for an ongoing hit-to-lead optimization campaign towards next-generation anti-cancer drugs.

Additionally, IGF2BP2 was found to bind to the m6A site in LDHA mRNA, thereby enhancing its stability. Overall, TFAP2A facilitated aerobic glycolysis and PC progression via IGF2BP2-mediated stabilization of LDHA mRNA, providing novel insights for PC therapy.

RNA immunoprecipitation confirmed that IGF2BP2 bound to MDK mRNA, and this binding was significantly diminished upon mutation of the top three predicted N6‑methyladenosine modification sites in MDK. These findings suggested that the IGF2BP2/MDK axis contributed to abnormal colonic epithelial proliferation under T2DM conditions and may represent a potential therapeutic target to reduce carcinoma risk in patients with diabetes.

Elevated JAK3 expression activates JAK3/STAT3 signaling, and phosphorylated STAT3 subsequently upregulates oncogenes (e.g., MYC) as well as sialyltransferase ST6GALNAC5-which directly increases cell membrane sialylation, a known driver of immune evasion. Our findings reveal the role of sialylation-immune-related lncRNAs in the immunosuppressive tumor microenvironment and cancer progression in ccRCC, providing a new framework for predicting patient outcomes and therapeutic responses.

Our systematic machine learning analysis demonstrates that m6A regulators can effectively predict CRC prognosis and immunotherapy response. The eight-gene signature provides a practical tool for clinical risk assessment and treatment decision-making.

Correspondingly, a combination of IGF2BP2 expression and Th17 cell numbers >10/mm2 in situ was associated with reduced recurrence-free survival. In summary, we unraveled a previously unknown molecular mechanism by which Th17 cells promote tumor progression under hypoxic conditions and suggest evaluation of Th17 cells as well as IGF2BP2 as potential target for therapeutic approaches in cervical cancer.

Moreover, 313 mRNAs, 55 lncRNAs, and 8 ncRNAs exhibited significant m6A methylation differences, overlapping with differentially expressed cancer-associated genes, particularly NUM, which was recently identified as a potential biomarker for PTC. These findings underscore the importance of m6A-related mechanisms and functions in PTC without AITD development and suggest that FN1-, NMU-, and LAMB3-associated pathways may be potential therapeutic targets and molecular mechanisms for this disease.

Collectively, our findings uncover that METTL3-mediated m6A modification of CACNA1E contributes to OS progression and chemoresistance through enhancing WNT7B-mediated non-canonical Wnt/Ca2+ signaling. Targeted inhibition of CACNA1E in combination with MTX may be a promising alternative therapeutic strategy for patients with MTX-resistant OS.

Rescue experiments confirms that STAT1 mediates IGF2BP2-driven dedifferentiation. The IGF2BP2-m6A-STAT1 complex is a master regulator of thyroid cancer dedifferentiation, establishing a novel therapeutic target for redifferentiation therapy in advanced thyroid cancer.

Functionally, overexpression of IGF2BP2 in skeletal muscle satellite cells (SMSCs) was associated with significant changes in the expression of several genes linked to muscle development and signaling pathways, including upregulation of IGF1, EGFR, FGF19, BMP6, BMP2, ACVR1C and WNT5A and downregulation of MYBPC3, NODAL, HOXD13, TNXB, and ADD2 (Padj < 0.01). Furthermore, protein-protein interaction (PPI) network analysis of these genes suggests that IGF2BP2 may coordinate key genes, contributing to its potential role in skeletal muscle development in geese.