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Abstract
MicroRNAs (miRNAs) play critical roles in hepatocellular carcinoma (HCC) progression and are key determinants of prognosis. In this study, we found that miR-425-5p was elevated in HCC and correlated with poor prognostic clinicopathological features and low post-operative long-term survival. Multivariate survival analysis indicated that miR-425-5p expression was an independent risk factor for overall and disease-free survival. Interestingly, miR-425-5p promoted invasion and metastasis by HCC cells, but not HCC cell proliferation or apoptosis in vitro. SCAI and PTEN were determined to be downstream targets of miR-425-5p. miR-425-5p-mediated effects were inhibited by ectopic expression of SCAI, and PTEN exhibited a smaller inhibitory effect. SCAI also suppressed PTEN expression. In addition, miR-425-5p promoted epithelial-to-mesenchymal transition (EMT), which was antagonized by SCAI. miR-425-5p also promoted HCC cell invasion and metastasis via SCAI-mediated dysregulation of integrin β1-Fak/Src-RhoA/CDC42, PTEN-AKT, and TIMP2-MMP2/MMP9 signaling. Finally, miR-425-5p promoted metastasis in a xenograft mouse model of HCC. These results indicate that miR-425-5p facilitates EMT and extracellular matrix degradation and promotes HCC metastasis through SCAI-mediated dysregulation of multiple signaling pathways. MiR-425-5p is therefore a potential prognostic biomarker and novel therapeutic target in HCC.
Highlights
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death in China [1]
MiR425-5p promoted metastasis in a xenograft mouse model of hepatocellular carcinoma (HCC). These results indicate that miR-425-5p facilitates epithelialto-mesenchymal transition (EMT) and extracellular matrix degradation and promotes HCC metastasis through SCAI-mediated dysregulation of multiple signaling pathways
We evaluated miR-425-5p expression in HCC tissue and adjacent non-tumor liver tissue (ANLT) from 110 HCC patients using quantitative real-time PCR
Summary
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death in China [1]. A better understanding of the events responsible for HCC metastasis is critical important for prevention and treatment. Many human miRNAs have been identified, and aberrant expression of these miRNAs plays essential roles in various physiological and pathological processes [5]. Previous studies have demonstrated that miRNAs play critical roles in HCC progression (e.g. cell proliferation and migration, apoptosis, and metastasis) [6,7,8,9,10]. The pathological relevance and significance of the majority of miRNAs in HCC metastasis are not yet clear. We investigated the potential clinical value of miR-425-5p in HCC. We evaluated miR425-5p function in HCC growth and metastasis using in vitro and in vivo models
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