L Chang1, K Li1, T Guo2. 1. Department of General Surgery, Zhongnan Hospital of Wuhan University, Donghu Road 169, 430071, Wuhan, People's Republic of China. 2. Department of General Surgery, Zhongnan Hospital of Wuhan University, Donghu Road 169, 430071, Wuhan, People's Republic of China. guotaosci@126.com.
Abstract
OBJECTIVE: To determine the role of miR-26a-5p in tumor invasion and metastasis in hepatocellular carcinoma (HCC). METHODS: We evaluated miR-26a-5p expression in HCC tissues by quantitative PCR and then analyzed its clinical significance using a Cox regression model. Transwell and nude mouse models were used to examine tumor metastasis in vitro and in vivo, respectively. The relationship between miR-26a-5p and epithelial-mesenchymal transition was also investigated by q-PCR and western blot. RESULTS: Strong downregulation of miR-26a-5p was observed in tumor tissues compared to paired adjacent normal tissues. Moreover, patients with low miR-26a-5p expression had a significantly poorer prognosis than those with high expression. The multivariate analysis indicated that miR-26a-5p expression was an independent prognostic indicator. The experimental transwell model and athymic mouse model revealed that miR-26a-5p depressed tumor metastasis in vitro and in vivo, respectively. In addition, the decreased miR-26a-5p level observed in HCC was associated with reduced E-cadherin expression and upregulation of vimentin, which affects the molecular mechanism of EMT. CONCLUSION: Downregulation of miR-26a-5p promotes tumor metastasis by targeting EMT and influences the prognosis of HCC patients. Therefore, miR-26a-5p has potential as a new biomarker and therapeutic target.
OBJECTIVE: To determine the role of miR-26a-5p in tumor invasion and metastasis in hepatocellular carcinoma (HCC). METHODS: We evaluated miR-26a-5p expression in HCC tissues by quantitative PCR and then analyzed its clinical significance using a Cox regression model. Transwell and nude mouse models were used to examine tumor metastasis in vitro and in vivo, respectively. The relationship between miR-26a-5p and epithelial-mesenchymal transition was also investigated by q-PCR and western blot. RESULTS: Strong downregulation of miR-26a-5p was observed in tumor tissues compared to paired adjacent normal tissues. Moreover, patients with low miR-26a-5p expression had a significantly poorer prognosis than those with high expression. The multivariate analysis indicated that miR-26a-5p expression was an independent prognostic indicator. The experimental transwell model and athymic mouse model revealed that miR-26a-5p depressed tumor metastasis in vitro and in vivo, respectively. In addition, the decreased miR-26a-5p level observed in HCC was associated with reduced E-cadherin expression and upregulation of vimentin, which affects the molecular mechanism of EMT. CONCLUSION: Downregulation of miR-26a-5p promotes tumor metastasis by targeting EMT and influences the prognosis of HCC patients. Therefore, miR-26a-5p has potential as a new biomarker and therapeutic target.
Authors: Vasily Vasko; Allan V Espinosa; William Scouten; Huiling He; Herbert Auer; Sandya Liyanarachchi; Alexander Larin; Victoria Savchenko; Gary L Francis; Albert de la Chapelle; Motoyasu Saji; Matthew D Ringel Journal: Proc Natl Acad Sci U S A Date: 2007-02-12 Impact factor: 11.205