CCCTC-binding factor regulates splicing factor proline and glutamine-rich to promote malignant growth of osteosarcoma.

Abstract

Objectives: CCCTC-binding factor (CTCF) is a candidate tumor regulatory gene that encodes multifunctional transcription factors. While its role in various cancers has been studied, its function and mechanism in osteosarcoma were uncertain. Previous studies have identified splicing factor proline and glutamine-rich (SFPQ) as an oncogene in osteosarcoma. Bioinformatic analysis suggested that CTCF may regulate SFPQ transcriptionally. This study aimed to elucidate the role of CTCF in osteosarcoma and explore its possible regulatory relationship with SFPQ.

Methods: Potential transcription factors of SFPQ were identified using an online transcription factor analysis database. The expression levels of CTCF in osteosarcoma cells were assessed using quantitative real-time PCR (qRT-PCR) and western blotting (WB). The effect of CTCF and SFPQ on osteosarcoma cell behavior was evaluated through cell function assays, dual-luciferase reporter assays, and rescue experiments.

Results: Database analyses (hTFtarget and GEPIA2) indicated a moderate correlation between CTCF and SFPQ. qRT-PCR and WB results confirmed significant CTCF expression in osteosarcoma cells. Overexpression of CTCF enhanced cell proliferation, migration, and invasion. Furthermore, CTCF was found to bind to the promoter region of SFPQ, leading to its upregulation. Rescue experiments demonstrated that SFPQ knockdown attenuated the oncogenic effects of CTCF overexpression.

Conclusions: CTCF functions as an oncogene in osteosarcoma by positively regulating SFPQ expression, thereby promoting the malignant properties of osteosarcoma cells. These findings suggest that targeting the CTCF-SFPQ axis may be a therapeutic strategy for osteosarcoma.