Targeting RBM39 suppresses tumor growth and sensitizes osteosarcoma cells to cisplatin

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Osteosarcoma is a common primary bone cancer with limited effective treatments.
• RNA-binding proteins (RBPs) play critical roles in cancer development and are emerging as potential therapeutic targets.
• The therapeutic potential of targeting RBPs in osteosarcoma remains largely unexplored.

Purpose of the Study:

• To investigate the role of RNA-binding protein 39 (RBM39) as a therapeutic target in osteosarcoma.
• To elucidate the molecular mechanisms by which RBM39 influences osteosarcoma progression and chemoresistance.
• To evaluate the efficacy of pharmacological RBM39 inhibition in combination with cisplatin for osteosarcoma treatment.

Main Methods:

• Identified RBM39 as a potential therapeutic target through expression analysis.
• Investigated RBM39's role in cell viability and its association with patient prognosis.
• Elucidated the molecular pathway involving RBM39, c-Jun, DKK1, and the GSK3β-NF-κB pathway.
• Assessed the efficacy of aryl sulfonamide E7820 in inhibiting RBM39 and its effect on osteosarcoma growth and cisplatin sensitivity in vitro and in vivo.

Main Results:

• RBM39 expression is elevated in osteosarcoma and correlates with poor patient prognosis.
• RBM39 acts as a coactivator for c-Jun, upregulating DKK1 and activating the GSK3β-NF-κB pathway.
• Pharmacological inhibition of RBM39 using aryl sulfonamide E7820 effectively suppressed osteosarcoma growth.
• RBM39 inhibition sensitized osteosarcoma cells to cisplatin treatment, both in vitro and in vivo.

Conclusions:

• RBM39 is a critical regulator of osteosarcoma cell viability and progression.
• Targeting RBM39 with aryl sulfonamides represents a promising therapeutic strategy for osteosarcoma.
• Combining aryl sulfonamides with cisplatin may offer a beneficial treatment approach for osteosarcoma patients.