Abstract 3349: A regulatory circuit HP1 gamma/miR-451a/c-Myc promotes prostate cancer progression

Abstract Heterochromatin protein 1 gamma (HP1 gamma), as a reader of the histone codes, is involved in the determination of higher order of chromatin structure. It has also been implicated in carcinogenesis of various cancer types. However, the role of HP1 gamma in prostate cancer (PCa) progression and the underlying molecular mechanisms remain largely unknown. Using the public microarray data from GEO and TCGA database, we found that HP1 gamma was upregulated in PCa, comparing with benign prostate tissues. PCa patients with higher level of HP1 gamma had shorter disease-free survival, indicating that HP1 gamma level can serve as prognostic marker in PCa patients (p = 0.016). In addition, depletion of HP1 gamma by shRNA in PCa cells not only repressed proliferation and induced apoptosis, but also impaired tumorigenicity in vitro and in vivo. We also found that c-Myc was capable of upregulating HP1 gamma by directly binding to the E-box element in the first exon of HP1 gamma gene, and the upregulated HP1 gamma, in turn, repressed the expression of miR-451a by enhancing H3K9 methylation at the promoter region of miR-451a. Furthermore, reduction of miR-451a significantly reversed HP1 gamma loss-induced PCa cell apoptosis, whereas miR-451a overexpression repressed cell survival by targeting and downregulating c-Myc. The association among mRNA and protein expression levels of c-Myc, HP1 gamma and miR-451a were further confirmed in human clinical samples using Spearman correlation analysis. Therefore, we propose that an HP1 gamma/miR-451a/c-Myc regulatory circuit exists in PCa cells and this circuit plays a crucial role in PCa progression. Citation Format: Ruimin Huang, Cunjie Chang, Jiakuan Liu, Xiaojing Huang, Lan Shen, Dianzheng Zhang, Jun Yan. A regulatory circuit HP1 gamma/miR-451a/c-Myc promotes prostate cancer progression [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 3349. doi:10.1158/1538-7445.AM2017-3349