TBP activates DCBLD1 transcription to promote cell cycle progression in cervical cancer

Abstract

Discoidin, CUB, and LCCL domain-containing (DCBLD) proteins have been associated with poor prognosis of human cancers. This study investigated the function of DCBLD1 in the development of cervical cancer (CC) and explored its associated mechanism. DCBLD1 was identified as a dysregulated gene in CC via bioinformatics analysis. Immunohistochemistry and RT-qPCR assays revealed increased DCBLD1 expression in CC specimens and cells. Artificial DCBLD1 knockdown blocked the proliferation, invasion, and migration of cells, while promoting cell apoptosis and inducing cell cycle arrest in the G1 phase. Following bioinformatic predictions and subsequent chromatin-immunoprecipitation and luciferase reporter assays, TATA-box binding protein (TBP) was found to be a transcription factor that binds to the DCBLD1 promoter region for transcriptional activation. Knockdown of TBP similarly blocked the malignant properties of CC cells and induced cell cycle arrest, but these changes were reversed by further DCBLD1 overexpression. Xenograft mouse tumors were generated for in vivo validation. Consistently, the tumorigenic activity of CC cells in nude mice was suppressed by TBP knockdown, but restored by DCBLD1 overexpression. In conclusion, this study provides novel evidence that TBP-mediated DCBLD1 activation is correlated with cell cycle and CC progression. TBP and DCBLD1 may serve as potential therapeutic targets for CC management.

Keywords: Cell cycle arrest; Cervical cancer; DCBLD1; TBP; Xenograft tumors.