SH3BP5-AS1/IGF2BP2/VDAC2 Axis Promotes the Apoptosis and Ferroptosis of Bladder Cancer Cells

Abstract

BACKGROUND: Bladder cancer (BC) is the most common malignant tumor in the urinary system with a high incidence, imposing a burden on the healthcare system worldwide. The participation of long non-coding RNAs (lncRNAs) in BC has attracted increasing attention. OBJECTIVE: The aim in the current study was to explore the potential mechanism involving SH3BP5-AS1 in modulating BC cell proliferation, apoptosis and ferroptosis. METHODS: qPCR and WB analysis measured the expression of RNAs and proteins. Functional and mechanism experiments were performed to investigate RNA impacts on cell proliferation, apoptosis and ferroptosis, and explore the correlation between RNA and protein expression. RESULTS: SH3BP5-AS1 was down-regulated in BC cells, and SH3BP5-AS1 overexpression could inhibit BC cell proliferation but facilitate the cell apoptosis. SH3BP5-AS1 was also found to facilitate the ferroptosis of BC cells. Additionally, SH3BP5-AS1 was confirmed to recruit IGF2BP2 to regulate VDAC2 expression in the m6A-dependent manner. VDAC2 was detected to be down-regulated in BC cells and was verified to inhibit BC cell growth. Moreover, it was indicated from rescue assays that SH3BP5-AS1 could modulate VDAC2 expression to promote the ferroptosis of BC cells. CONCLUSION: SH3BP5-AS1 could affect BC cell proliferation, apoptosis and ferroptosis via IGF2BP2/VDAC2, providing a novel molecular perspective for understanding BC.