ELAVL1-Regulated Bone Morphogenetic Protein 2 as a Predictive Biomarker for Ultrasound Therapy Response in Oral Squamous Cell Carcinoma Bone Infiltration.

Abstract

Background: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the neck and head region. A major contributor to poor prognosis in OSCC is bone infiltration. Bone morphogenetic protein 2 (BMP2), known to promote tumor progression and bone metastasis in several cancers, has recently emerged as a potential molecular mediator of OSCC invasiveness. However, its role in predicting therapeutic response-particularly in emerging modalities like ultrasound-based therapies-remains unexplored. Methods: The authors assessed BMP2 expression in OSCC tissues and cell lines using RT-qPCR. Functional assays were conducted to evaluate malignant cellular behaviors, including proliferation and epithelial-mesenchymal transition (EMT). Osteoclast differentiation and bone resorption were quantified via TRAP staining and resorption pit assays. RNA-binding interactions were identified using RNA immunoprecipitation and biotin pull-down assays. Results: BMP2 was significantly overexpressed in OSCC and strongly correlated with bone infiltration. Its upregulation enhanced OSCC cell proliferation, EMT, and osteoclast-mediated bone resorption. In vivo, BMP2 knockdown suppressed tumor growth and bone invasion. Mechanistically, the authors identified ELAVL1 as a key RNA-binding protein that stabilized BMP2 transcripts, thereby promoting its expression. Moreover, BMP2 overexpression rescued the tumor-suppressive effects of ELAVL1 silencing, highlighting a critical regulatory axis. Given the role of BMP2 in modulating the tumor microenvironment and its association with bone-invasive phenotypes, it holds potential as a predictive biomarker for response to ultrasound-enhanced therapeutic strategies. Conclusions: ELAVL1-regulated BMP2 promotes OSCC progression and bone infiltration and may serve as a valuable predictive biomarker for therapeutic response in ultrasound-guided biotherapies.