MiR-425-5p promotes invasion and metastasis of hepatocellular carcinoma cells through SCAI-mediated dysregulation of multiple signaling pathways
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Feng Fang1, Tianqiang Song1, Ti Zhang1, Yunlong Cui1, Gewen Zhang2 and Qingqing Xiong1
1Department of Hepatobiliary Cancer, Tianjin Medical University Cancer Institute and Hospital, Ti-Yuan-Bei, Tianjin 300060, China
2Department of Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
Feng Fang, email: firstname.lastname@example.org
Gewen Zhang, email: email@example.com
Keywords: miR-425-5p, hepatocellular carcinoma, SCAI, PTEN, integrin β1
Received: October 31, 2016 Accepted: February 13, 2017 Published: March 07, 2017
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.
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