Deciphering the crucial role of IGF2BP3 in modulating stemness traits of salivary adenoid cystic carcinoma.

Abstract

Salivary adenoid cystic carcinoma (SACC) is a rare yet clinically vexing malignancy characterized by perineural invasion, late lung-dominant metastasis, and limited systemic options, underscoring the need for mechanistic targets specific to SACC. This study employs a systematic experimental approach to elucidate the functional role and regulatory mechanisms of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in SACC cells. Initial validation confirmed elevated IGF2BP3 expression in SACC tumor tissue, with knockdown of IGF2BP3 markedly suppressing cell proliferation, clonogenicity, and migratory capacity in SACC cells. Subsequent RNA sequencing analysis revealed the downregulation of stemness pathways upon IGF2BP3 knockdown, corroborating its regulatory role in SACC stemness. Leveraging single-cell sequencing data, we corroborated the association between IGF2BP3 and stemness traits within SACC cells. In vivo experiments further demonstrated that IGF2BP3 knockdown attenuated SACC tumor growth. In summary, this study provides a comprehensive understanding of IGF2BP3's function and regulatory mechanisms in SACC, offering vital theoretical support for future targeted therapeutic strategies involving IGF2BP3.