miR-515–5p suppresses HCC migration and invasion via targeting IL6/JAK/STAT3 pathway

MicroRNAs (miRNAs) have been identified as critical modulators of cell migration and invasion, which are the major causes of cancer progression including hepatocellular carcinoma (HCC). However, the accurate role of miR-515–5p in HCC is still uncertain. Here, we report that miR-515–5p expression is down-regulated in HCC tissues and cell lines, and associated with absence of capsule formation (p = 0.015)﹑microvascular invasion(p = 0.003)﹑and advantange TNM stage (II-III) (p = 0.014) in HCC patients. Overexpression of miR-515–5p inhibited migration and invasion of HCC cells in vitro and in vivo, while miR-515–5p knockdown has the inverse effect. Moreover, using miRNA databases and dual-luciferase report assay, we find miR-515–5p directly binds to the 3′-untranslated region (3′-UTR) of interleukin 6 (IL6). In addition, the regulatory association between miR-515–5p and the IL-6/Janus kinase (JNK)/signal transducer and activator of transcription-3 (STAT3) signaling pathway was explored. Furthermore, overexpression of miR-515–5p inhibited the activation of the JAK/STAT3 signaling pathway, which was rescued by overexpression of IL-6. The results of the current study indicate that miR-515–5p overexpression may serve an important role in inhibiting migration and invasion of HCC cells via suppression of IL-6/JAK/STAT3 signaling pathway activation. MiR-515–5p may serve as a potential therapeutic target for HCC. •Down-regulation of miR-515–5p is associated with the metastatic properties of HCC.•Low miR-515–5p expression indicated poor prognosis of HCC.•miR-515–5p inhibits HCC metastasis in vitro and vivo.•IL6 was the direct target of miR-515–5p.•miR-515–5p targets IL6 to further inhibit the activation of JAK/STAT3 pathwayin HCC.