IGF2BP3 as a Prognostic Biomarker and Regulator of Metastasis in Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is an aggressive skin cancer with frequent development of metastases, however effective treatment options for advanced disease are often missing. In this study, we investigated the clinical significance and functional impact of the Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in MCC. Our results revealed elevated IGF2BP3 expression in metastases as compared to primary tumors. High IGF2BP3 levels in primary MCCs were associated with shorter disease-specific survival. In an MCC xenograft model, lung metastases exhibited increased IGF2BP3 expression. Functional studies showed that IGF2BP3 primarily regulates cell migration and invasion in MCC. We identified 281 direct RNA targets of IGF2BP3 with enriched functions linked to metastasis-related processes and several targets overlapped with genes differentially expressed between MCC primary tumors and metastases, implying that IGF2BP3 and its targets contribute to tumor progression. Inhibition or silencing of bromodomain-containing protein 4 (BRD4) reduced IGF2BP3 expression, suggesting BRD4 as a potential regulator of IGF2BP3. Our study underscores the role of IGF2BP3 in MCC metastasis and its potential as a prognostic biomarker. We conducted RNA immunoprecipitation followed by RNA sequencing (RIP-seq) in WaGa cells, using IGF2BP3 or IgG (negative control) antibody, with three independant replicates.