Presentation Authors: Zonghao You*, Chunhui Liu, Can Wang, Bin Xu, Nanjing, China, People's Republic of, Han Guan, Bengbu, China, People's Republic of, Ming Chen, Nanjing, China, People's Republic of
Introduction: Accumulated evidence indicates that CCAT1 functions as an oncogene in the progression of a variety of tumors. However, little is known as to how CCAT1 impacts tumorigenesis in human prostate cancer.Our purpose is to explore the role of CCAT1 in the malignant progression of prostate cancer and the mechanism of the influence.
Methods: Employing qRT-PCR, ISH, and a re-analysis of The Cancer Genome Atlas (TCGA) and The Memorial Sloan Kettering Cancer Center (MSKCC) data, we compared CCAT1 expression between castration-resistant prostate cancer (CRPC) tissues and androgen dependent prostate cancer (ADPC) tissues. Kaplan-Meier method was applied to analysis the prognostic value. The impacts of CCAT1 on biological function were evaluated by in vitro assays and in vivo nude mice model. RNA pulldown, RIP and ChIP-qPCR assays were adopted to explore the regulatory mechanisms of CCAT1 in the progression of CRPC.
Results: CCAT1 could promote PCa cell proliferation and accelerate the tumor growth of PCa xenografts. At a molecular level, CCAT1 sponged miR-28-5p to reverse the anti-cancer effect. Additionally, RNA pulldown, RIP and ChIP-qPCR assays revealed CCAT1 acts as a scaffold for DDX5 (P68) and the AR transcriptional complex, thus stimulating CRPC progression.
Conclusions: Our findings indicated CCAT1 acts as one of oncogenic factors in the progression of CRPC by performing different regulatory mechanisms in the nucleus and cytoplasm of cells.
Source of Funding: This study was funded by The National Natural Science Foundation of China (No. 81872089, 81370849, 81300472, 81070592, 81202268, 81202034), Natural Science Foundation of Jiangsu Province (BK 20150642), National Science Foundation of Anhui Province (KJ2018