SULF1 promotes malignancy potential of cervical cancer by activating VEGFR2/PI3K/AKT signaling pathway

Abstract Purpose Identifying novel molecular targets remains essential in molecular targeted therapy for cervical cancer patients with advanced stage or reccurrence. Our study aims to investigate the precise roles and regulatory mechanism underlying SULF1 in the initiation and progression of cervical cancer (CC). Methods The expression and prognostic values of SULF1 in cervical cancer were analyzed through bioinformatics analysis, RT-PCR, immunohistochemistry and western blot assays. The function of SULF1 in proliferation, migration and invasion of cervical cancer cells through lentivirus transduction, CCK8, flow cytometry analysis, plate colony formation assay, scratch assay, Transwell assay and mouse models. Bioinformatics analysis and western blot assay were employed to identify the significant signaling pathways associated with SULF1 in cervical cancer. Results SULF1 expression was significantly upregulated in CC tissues, which was associated with poor prognosis of patients with CC. In vitro , the upregulation of SULF1 expression in cervical cancer HeLa cells promoted cell proliferation, colony formation, migration and invasion while inhibiting cell apoptosis. Conversely, downregulation of SULF1 expression had the opposite effect. In vivo . the upregulation of SULF1 expression resulted in a significant increase in both tumor growth and angiogenesis, while its downregulation had the opposite effect. Bioinformatics analysis, western blot detection and cell function rescue assay confirmed that the upregulation of SULF1 in HeLa cells promoted cellular tumorigenic behaviors by activating the VEGFR2/PI3K/AKT signaling pathway. Conclusion SULF1 plays an oncogenic role in the tumorigenesis and development of CC, indicating its potential as a novel molecular target for gene-targeted therapy in patients with CC.