Abstract 1387: Target RNA sequencing revealed the expression profile of cancer genes in response to deacetylase inhibitor in primary culture of prostate cancer cells
Authors: Hong Yin, Adam H. Greer, Glenn Mills
Journal: Cancer Research (2017)

Abstract Histone acetylation is a dynamic event to optimize cell functions through the control of RNA transcription and gene expression. In cancer, the histone deacetylation is a therapeutic target. Suppression of histone deacetylase increased the growth arrest, apoptosis, and senescence in cancer cells. Several histone deacetylase inhibitors (HDACis) have been developed and applied as a target therapy of various types of cancer, including the prostate cancer. However, the altered gene expression in HDACis treated prostate cancer cells is less reported. Little is known about the gene expression profiles of primary cultures of prostate cancer. In this study, we examined the cancer gene expression profile in primary cultures of human prostate cancer. Cells were isolated from two patient’s prostate cancer samples. Isolated cells were cultured in prostate epithelium culture medium CnT-52. After 24 hours of exposure to 400nM of Trichostatin A (TSA), an inhibitor of histone deacetylase I and II. RNA was extracted and quantified. The library was prepared with Illumina’s TruSight RNA Pan-Cancer Panel. The sequencing was performed on NextSeq 500 platform with NextSeq 500/550 mid output v2 kit (150cycles). FastQ files were generated by BaseSpace Onsite and analyzed further by TopHat alignment (Illumina) and Partek Flow (Partek). The Trusight RNA Pan-Cancer panel targets 1385 cancer genes and covers 21043 exonic regions with 57010 probes. The results showed that 59 of the 1385 cancer genes were significantly changed (FDR p-value&amp;lt;0.05, fold change &amp;gt;4 fold) in TAS treated cells. In the treated cells 49 genes were unregulated and 10 genes were down-regulated. The altered expression of 59 genes is involved in multiple cell functions. Genes that were upregulated included apoptosis associated genes (MAP2K6 and BIRC3), tumor suppression genes (DIRAS3, PEG3, PTPRO, and DNM3), and P53-target gene (CYFIP2). The genes that were down-regulated included cell cycle regulation genes (CDK1 and CCNA2), DNA damage response genes (BRCA1 and BRIP1), as well as cell proliferation marker Ki67 gene (MKI67). However, the gene expression response to TSA is complicated. Some altered gene expression favors tumor growth and progression while other gene expression changes inhibit tumor growth and promote apoptosis. In conclusion, we identified the gene profile in primary culture of prostate tumor in response to a histone deacetylase inhibitor, TSA. The therapeutic effects of HDACis could be influenced by the summation of contradicting tumor promoting and suppression gene expression profile changes. Citation Format: Hong Yin, Adam H. Greer, Glenn Mills. Target RNA sequencing revealed the expression profile of cancer genes in response to deacetylase inhibitor in primary culture of prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1387. doi:10.1158/1538-7445.AM2017-1387