Abstract 1521: Role of Trim28 in prostate cancer

Abstract

Abstract TRIM28 is an essential gene during embryonic development, which is involved in a wide range of biologic processes. From the pathologic viewpoint, TRIM28 overexpression was proved to broadly exist in pancreatic, liver, breast, glioma and lung cancer, and often expression of TRIM28 is correlated with clinical stage. Functional assays have demonstrated that TRIM28 promotes cancer cell growth and metastasis, further supporting TRIM28 as a promising target for therapeutic intervention. For past decade, TRIM28 is considered to be a transcriptional co-repressor due to TRIM28-dependent recruitment of histone modifiers such as CHD1/NuRD complex and SETDB1 for histone methylation and heterochromatin formation to achieve gene silencing. Surprisingly, transcriptome study revealed that TRIM28 can activate the expression of its target genes as much as it represses, hypothesizing the main role of TRIM28 may not lie in transcriptional repression. In addition, recent findings demonstrated that TRIM28 interacts with 7SK snRNP complex, which facilitates P-TEFb kinase module recruitment and productive transcription elongation at inducible genes. This evidence implicated that TRIM28 may form distinct complexes to induce or repress gene expression in context-dependent manner. On top of that, it remains unclear about the role of TRIM28 in prostate cancer. Our preliminary study revealed that TRIM28 is upregulated in castration-resistant prostate cancer (CRPC). TRIM28 knockdown markedly decreased prostate cancer cell proliferation, clonogenicity as well as CRPC-xenograft tumor growth. Moreover, proteomic analysis in LNCaP prostate cancer cells revealed that TRIM28 associates with a number of transcription co-activators. Gene expression profiling showed that androgen signaling is positively regulated by TRIM28. We proposed that TRIM28 forms the transcription activation complexes that modulate gene expression of various oncogenic pathway and promote PCa progression. Citation Format: Ka-Wing Fong, Jonathan Zhao, Bin Zheng, Jindan Yu. Role of Trim28 in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1521.