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

Yan Li; Dan Xu; Chunyang Bao; Yuannv Zhang; Di Chen; Fangyu Zhao; Jie Ding; Linhui Liang; Qifeng Wang; Li Liu; Jinjun Li; Ming Yao; Shenglin Huang; Xianghuo He

doi:10.18632/oncotarget.2965

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

Oncotarget. 2015 Feb 10;6(4):2421-33. doi: 10.18632/oncotarget.2965.

Authors

Yan Li¹, Dan Xu¹, Chunyang Bao¹, Yuannv Zhang¹, Di Chen¹, Fangyu Zhao¹, Jie Ding², Linhui Liang², Qifeng Wang², Li Liu², Jinjun Li¹, Ming Yao¹, Shenglin Huang², Xianghuo He^{1

2}

Affiliations

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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blotting, Western
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Cell Cycle Proteins
Cell Line, Tumor
Cell Movement / genetics
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
Female
GPI-Linked Proteins / genetics*
GPI-Linked Proteins / metabolism
GTPase-Activating Proteins
Gene Expression Regulation, Neoplastic
HEK293 Cells
Heat Shock Transcription Factors
Hep G2 Cells
Humans
Liver Neoplasms / genetics*
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Male
MicroRNAs / genetics*
Microscopy, Confocal
Middle Aged
Neoplasm Invasiveness
Neoplasm Metastasis
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors / genetics*
Transcription Factors / metabolism

Substances

Cell Cycle Proteins
DNA-Binding Proteins
EVI5 protein, human
GPI-Linked Proteins
GTPase-Activating Proteins
HSF1 protein, human
Heat Shock Transcription Factors
MIRN135 microRNA, human
MicroRNAs
Nuclear Proteins
RECK protein, human
Transcription Factors