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Int J Clin Exp Pathol 2013;6(12):2864-2871

Original Article
KAT5 and KAT6B are in positive regulation on cell proliferation of prostate cancer
through PI3K-AKT signaling

Wei He, Min-Guang Zhang, Xiao-Jing Wang, Shan Zhong, Yuan Shao, Yu Zhu, Zhou-Jun Shen

Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

Received October 6, 2013; Accepted November 1, 2013; Epub November 15, 2013; Published December 1, 2013

Abstract: Histone modifications play important roles in the tumorigenesis and progression of prostate cancer (PCa) and genes involved in
histone modifications are seemed as ideal targets for treatment of PCa patients. However, clinical trials have shown that those existing drugs
exert the minimal antitumor activity and excess adverse effects on PCa patients. Therefore, it is of great interest to figure out novel specific
biomarkers to guide the development of new drugs. In present study, an RNAi screening with 44 genes involved in histone modifications was
applied to a PCa cell line, Du145. The results showed that nine genes were in positive regulation of Du145 cell growth. Then four selected
genes (KAT2B, KAT5, KAT6B and HDAC1) were found to exert this effect by a gene-specific manner when silenced. And then KAT5 or KAT6B
silenced cells were subjected to DNA microarray analysis. The common differentially expressed genes were analyzed by Ingenuity Pathway
Analysis (IPA) and found that PDEF signaling, EIF2 signaling and PI3K signaling was suppressed following by KAT5 or KAT6B silencing.
Subsequent immunoblotting assay showed that AKT signaling was inhibited, which suggested that KAT5 or KAT6B regulates cancer cell
growth through PI3K-AKT signaling. Together with our published data [31] that AURKA inhibitoin increased drug sensitivity of DU145, our work
demonstrated the underlying mechanism that how the acetylation enzyme regulates cancer cells survial and might provide potential therapeutic
targets for prostate cancer patients in future epigenetic drug development. (IJCEP1310016).

Keywords: Prostate cancer, histone modifications, RNAi screening, KAT5, KAT6B, PI3K-AKT signaling

Address correspondence to: Dr. Zhou-Jun Shen, Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University,
Shanghai, China. E-mail: shenzhoujun6@163.com