MicroRNA-135b, a HSF1 target, promotes tumor invasion and metastasis by regulating RECK and EVI5 in hepatocellular carcinoma

Abstract

// Yan Li 1,* , Dan Xu 1,* , Chunyang Bao 1,* , Yuannv Zhang 1 , Di Chen 1 , Fangyu Zhao 1 , Jie Ding 2 , Linhui Liang 2 , Qifeng Wang 2 , Li Liu 2 , Jinjun Li 1 , Ming Yao 1 , Shenglin Huang 2 and Xianghuo He 1,2 1 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China 2 Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China * These authors contributed equally to this work Correspondence: Xianghuo He, email: // Shenglin Huang, email: // Keywords : MicroRNA-135b; RECK; EVI5; HSF1; Hepatocellular Carcinoma Received : September 24, 2014 Accepted : December 10, 2014 Published : December 11, 2014 Abstract MicroRNAs (miRNAs) often localize to chromosomal fragile sites and are associated with cancer. In this study, we screened for the aberrant and functional miRNAs in the regions of copy number alterations (CNAs) in hepatocellular carcinoma (HCC), and found that miR-135b was frequently amplified and upregulated in HCC tissues. The expression level of miR-135b was inversely correlated with the occurrence of tumor capsules. In addition, miR-135b promoted HCC cell migration and invasion in vitro and metastasis in vivo . The reversion-inducing-cysteine-rich protein with kazal motifs (RECK) and ecotropic viral integration site 5 (EVI5) were identified as the direct and functional targets of miR-135b in HCC. Furthermore, we observed that heat shock transcription factor 1 (HSF1) directly activated miR-135b expression, consequently enhancing HCC cell motility and invasiveness. The newly identified HSF1/miR-135b/RECK&EVI5 axis provides novel insight into the mechanisms of HCC metastasis, which may facilitate the development of new therapeutics against HCC.