SOX4 as a Key Oncogene Driving Tumor Invasion in Retinoblastoma

Area of Science:

• Ophthalmology
• Molecular Biology
• Oncology

Background:

• Retinoblastoma (RB) is a pediatric eye cancer.
• Understanding the molecular mechanisms driving RB invasion is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role of SRY-related HMG box transcription factor 4 (SOX4) in promoting retinoblastoma (RB) invasion.
• To elucidate the underlying oncogenic pathways involved in SOX4-mediated RB invasion.

Main Methods:

• SOX4 expression was analyzed in RB tissues and cell lines using bulk and single-cell RNA sequencing (RNA-seq, scRNA-seq).
• SOX4 was knocked down in RB cell lines (Y79, WERI-RB1) to assess functional changes via CCK-8, EdU, colony formation, and transwell assays.
• An orthotopic xenograft model was used to evaluate the in vivo effects of SOX4 knockdown on tumor invasion. Downstream pathways were analyzed by RNA-seq.

Main Results:

• SOX4, E2F3, and DEK were upregulated in RB tissues, with SOX4 elevated in extraocular RB, particularly in MKI67+ cells.
• SOX4 knockdown reduced RB cell proliferation, colony formation, and migration, and reversed epithelial-to-mesenchymal transition markers.
• In vivo, SOX4 knockdown decreased tumor invasion. RNA-seq identified alterations in Wnt/β-catenin and cyclin D1 signaling pathways.

Conclusions:

• SOX4 is a critical driver of local invasion in retinoblastoma.
• Targeting SOX4 presents a potential therapeutic strategy for RB by inhibiting invasion.
• Further research into SOX4's role may uncover novel molecular mechanisms for improved RB treatment.