IGF2BP3-mediated stabilization of RHOA mRNA promotes osteosarcoma proliferation via Hippo signaling

Osteosarcoma (OS) is the most common primary bone malignancy with an incompletely understood pathogenesis. The RNA-binding protein (RBP) insulin-like growth factor 2 messenger RNA (mRNA)-binding protein 3 (IGF2BP3) has been implicated in various cancers, but its role and underlying mechanisms in OS have not been fully elucidated. This study aimed to investigate the molecular function of IGF2BP3 in OS progression and elucidate its mechanisms.

The expression of IGF2BP3 was analyzed in OS tissues and cell lines. Functional assays, including cell proliferation and apoptosis analyses, were performed following IGF2BP3 silencing in OS cells. Mechanistic studies involving RNA immunoprecipitation and luciferase reporter assays were conducted to identify IGF2BP3 targets. In addition, quantitative real-time polymerase chain reaction (qRTPCR) and Western blotting were employed to detect the expression of target mRNAs and proteins.

IGF2BP3 was significantly overexpressed in OS and associated with poor patient outcomes. Its silencing suppressed OS cell proliferation and induced apoptosis. Mechanistically, IGF2BP3 was found to bind to and stabilize Ras homolog family member A (RHOA) mRNA leading to increased RHOA expression and subsequent activation of the Hippo pathway effector yes-associated protein (YAP).

IGF2BP3 promotes OS progression by stabilizing RHOA mRNA and activating the YAP signaling pathway, indicating its potential as a prognostic biomarker and therapeutic target.