DNA hypomethylation modification promotes BST2 expression in cervical cancer by facilitating STAT1 binding to the promoter of BST2.

Abstract

Cervical cancer (CC) is a common cancer that causes considerable morbidity and mortality, especially in developing countries. Bone marrow stromal cell antigen 2 (BST2) is a transmembrane glycoprotein, and its promoter methylation has been extensively documented in numerous human cancers. Nevertheless, the specific role of BST2 in CC remains unclear. This research utilized methylation-specific PCR (MSP), Western blotting, and RT-qPCR to evaluate the expression and DNA methylation levels of BST2 in CC tissues and cells. The role of STAT1 in regulating BST2 transcription was confirmed through dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays. Furthermore, we conducted experiments on cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), and xenograft tumor models to investigate the functional role and regulatory mechanisms of BST2 in CC, both in vitro and in vivo. We found that BST2 was increased in CC tissues and cells, promoting cell proliferation and EMT while inhibiting apoptosis. Mechanistically, BST2 upregulation was associated with hypomethylation of its promoter, potentially regulated by DNMT3a and DNMT3b. Furthermore, the transcription factor STAT1 was found to bind to the BST2 promoter, positively regulating its expression and thereby accelerating tumorigenesis in CC. Silencing BST2 significantly reduced tumor growth in vivo. Our findings highlight BST2 as a potential biomarker and therapeutic target in CC, with its expression regulated by DNA methylation and STAT1 binding.