Stichopus japonicus acidic mucopolysaccharide (SJAMP) exerts the tumor-suppressive activity in cervical cancer by targeting TFAP2A to downregulate CENPW
摘要
Cervical cancer (CC) remains a leading cause of cancer-related mortality among women, and advances in its therapeutic approaches are disappointing, in which novel therapies and precise experimental approaches are needed to be exploited. This study intends to explore the effects and involved molecular mechanism of Stichopus japonicus acidic mucopolysaccharide (SJAMP) on CC progression. CCK8 and EdU assays were utilized to test the ability of cell proliferation. Colony formation, transwell, flow cytometry assays were applied to detect cell colonies, migration, invasion, and apoptosis accordingly. RT-qPCR and western blot were used to quantify the expression levels of transcription factor AP-2 Alpha (TFAP2A) and centromere protein W (CENPW), respectively. JASPAR website, ChIP-qPCR, and dual-luciferase reporter assay were used to verify the binding loci of TFAP2A on the promoter region of CENPW. Xenograft tumor models were produced to confirm the effects of CENPW silence or SJAMP treatment in CC. SJAMP suppressed malignant phenotypes of CC cells in a dosage-dependent manner. Besides, SJAMP regulated the biological behaviors of CC cells via regulating TFAP2A expression, which further regulated CENPW expression as its transcription factor. The expression of CENPW was elevated in CC and positively correlated with TFAP2A, and the silence of CENPW hampered tumor growth in vivo. In addition, CENPW overexpression abolished the repressed cell malignant activities induced by TFAP2A silence. Xenograft tumor models proved that SJAMP curbed tumor growth in vivo via repressing TFAP2A-mediated CENPW expression. Our research revealed that SJAMP exerted its anti-tumor effects via decreasing TFAP2A-mediated CENPW expression in CC.
Graphical abstract