Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase

• DOI: 10.18632/oncotarget.3192
• Publication Date: 2015-09-15T06:35:44Z
• Authors: Ke Li; Jun Pang; Huaiyan Cheng; Wei-Peng Liu; Jin-Ming Di; Heng-Jun Xiao; Yun Luo; Hao Zhang; Wen-Tao Huang; Ming-Kun Chen; Liao-Yuan Li; Chun-Kui Shao; Ying-Hong Feng; Xin Gao
• Keywords: Male; 0301 basic medicine; Mice, Inbred BALB C; Muscle Proteins; Nerve Tissue Proteins; DNA Methylation; Prognosis; Transfection; 3. Good health; Mice; Prostatic Neoplasms, Castration-Resistant; 03 medical and health sciences; HEK293 Cells; Cell Line, Tumor; COS Cells; Chlorocebus aethiops; Animals; Humans; Neoplasm Metastasis; Promoter Regions, Genetic; DNA Modification Methylases

// Ke Li 1, * , Jun Pang Huaiyan Cheng 2, Wei-Peng Liu 3 Jin-Ming Di 1 Heng-Jun Xiao Yun Luo Hao Zhang Wen-Tao Huang Ming-Kun Chen Liao-Yuan Chun-Kui Shao 4 Ying-Hong Feng 2 Xin Gao Department of Urology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China Pharmacology, Uniformed Services University Health Sciences, Bethesda MD20814, USA First Hospital Nan Chang Nanchang 330006, Pathology, These authors have contributed equally to this work Correspondence to: Gao, e-mail: [e-mail] Feng, [e-mail] Keywords: prostate cancer, metastasis, transcription activator-like effectors (TALEs), CRMP4, epigenetic manipulation Received: December 15, 2014 Accepted: January 25, 2015 Published: April 09, ABSTRACT Prostate cancer is most commonly diagnosed non-cutaneous and one leading causes death for North American men. Whereas localized can be cured, there currently no cure metastatic cancer. Here we report a novel approach that utilizes designed chimeric (dTALEs) control metastasis. Transfection dTALEs DNA methyltransferase or demethylase induced artificial, yet active locus-specific CpG subsequent histone modifications. manipulations markedly altered expression endogenous metastasis suppressor gene. Remarkably, demethylation CRMP4 promoter in PC3 cells abolished whereas methylation non-metastatic 22Rv1 CRMP4-mediated suppression was found require activation Akt/Rac1 signaling down-regulation MMP-9 expression. This proof-of-concept study with epigenomic validates selected gene as an independent biomarker diagnosis prognosis opens up avenue mechanistic research on biology.