Ruocheng Xu
Research Mentor: Yihan Liu
Mentor Department: Department of Pathology, Parolia lab, Medicine
Author(s): Ruocheng Xu, Yihan Liu, Honglin Zhong, Calvin Burns, Abhijit Parolia
Session: Session 7 (4:00 PM – 4:50 PM)
Presentation Type: Poster 2
Abstract
Prostate cancer is the most commonly diagnosed cancer in the U.S. male population. Prostate cancer progression is driven by aberrant transcription programs, including oncogenic androgen receptor (AR) signaling. However, the cofactor genes that regulate oncogenic AR signaling remain to be characterized. Through a CRISPR screen, we identified that TFAP2C, a transcription factor, plays important roles in regulating AR signaling pathways and facilitating the proliferation of prostate cancer. The activity of transcription factors within cells exhibits dynamic and highly transient regulatory patterns. Therefore, this project aims to develop a degron system for TFAP2C in order to investigate the effect of TFAP2C acute loss in prostate cancer cells. To construct the degron model, we knocked out the endogenous TFAP2C gene, exogenously overexpressed TFAP2C tagged with the mAID system, and then treated with IAA to induce degradation. Upon IAA treatment, we observed an acute loss of TFAP2C within 4 hours, which is followed by a decrease in AR expression and its downstream signaling, as well as a decrease in cell proliferation hallmark genes. These effects were analyzed by measuring the levels of target proteins at different time intervals through western blotting and interrogating the levels of target RNA through RNA-seq. Moreover, through CellTiter-Glo luminescent cell viability assay, we observed attenuation in prostate cancer cell proliferation upon TFAP2C loss. Through establishing the degron model, this study reveals that acute loss of TFAP2C leads to the attenuation of AR expression and AR downstream signaling. Furthermore, this model allows us to further explore the transcription machinery dynamics in prostate cancer cells upon acute loss of TFAP2C and understand the oncogenic role of TFAP2C in this disease.
