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

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.