CUX2 prevents the malignant progression of gliomas by enhancing ADCY1 transcription.

ABSTRACT

Gliomas are one of the most prevalent brain tumors. This study sought to elucidate the mechanism of CUX2 in glioma development via ADCY1. CUX2 and ADCY1 expression in glioma predicted by bioinformatics analysis. Subsequent to gain- and loss-of-function experiments in glioma cells, cell proliferation was tested by CCK8 and plate clone formation assays, and cell migration and invasion by Transwell assay. The binding between CUX2 and ADCY1 was examined with dual-luciferase gene reporter and ChIP assays. The xenograft mouse model was established to verify the effect of the CUX2/ADCY1 axis on glioma cell growth in vivo. CUX2 and ADCY1 expression was low in glioma. The overexpression of CUX2 repressed the proliferative, migrating, and invasive abilities of glioma cells. Moreover, CUX2 was enriched in the ADCY1 promoter to enhance ADCY1 expression. ADCY1 upregulation diminished glioma cell proliferative, migrating, and invasive properties. Silencing of ADCY1 abrogated and upregulation of ADCY1 promoted the inhibitory influence of CUX2 upregulation on the malignant behaviors of glioma cells in vitro and gliomas cell growth in vivo. Collectively, CUX2 promoted ADCY1 transcription to delay glioma cell migration, proliferation, and invasion.