Shu Yang1,2, Hongying Zhang1, Hua Yang3, Jin Zhang1, Jiao Wang4, Ting Luo5, Yangfu Jiang6, Hui Hua7. 1. Laboratory of Oncogene, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. 2. Department of Abdominal Oncology, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China. 3. Department of Pathology, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China. 4. School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China. 5. Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. 6. Laboratory of Oncogene, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. jyangfu@scu.edu.cn. 7. Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. huahuihuaxi@163.com.
Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the common cancers that are very aggressive. The secreted cytokine transforming growth factor-β (TGF-β) promotes cancer metastasis by multiple mechanisms such as epithelial-mesenchymal transition and immune evasion. The canonical TGF-β signaling is largely mediated by smooth muscle actin/mothers against decapentaplegic (SMAD) proteins. The current study aims to explore the regulation of TGF-β/SMAD signaling by selenophosphate synthetase 1 (SEPHS1). METHODS: Immunohistochemistry was used to detect the expression of SEPHS1 in HCC and adjacent liver tissues. Western blotting and quantitative reverse-transcription PCR were used to detect the protein and mRNA levels in HCC cell lines. Cell migration and invasion were determined by transwell assay. Bioinformatic analysis was conducted to determine SEPHS1 expression in HCC and its correlation with the survival of HCC patients. RESULTS: Here we report that SEPHS1 is a positive regulator of SMAD proteins. SEPHS1 expression is up-regulated in HCC compared with adjacent liver tissues. SEPHS1 knockdown leads to decreased expression of SMAD2/3/4 and mesenchymal markers including snail, slug and N-cadherin in HCC cells. Furthermore, SEPHS1 knockdown results in a decrease in HCC cells migration and invasion, and suppresses the stimulation of HCC cells migration and invasion by TGF-β. Overexpression of SEPHS1 in HCC cells promotes cell invasion, which can be abrogated by SMAD3 knockdown. Lastly, higher expression of SEPHS1 is correlated with poor prognosis in HCC patients, as manifested by decreased overall survival and disease-free survival. CONCLUSIONS: SEPHS1 is a positive regulator of TGF-β/SMAD signaling that is up-regulated in HCC. Increased SEPHS1 expression may indicate poor prognosis for patients with HCC.
BACKGROUND:Hepatocellular carcinoma (HCC) is one of the common cancers that are very aggressive. The secreted cytokine transforming growth factor-β (TGF-β) promotes cancer metastasis by multiple mechanisms such as epithelial-mesenchymal transition and immune evasion. The canonical TGF-β signaling is largely mediated by smooth muscle actin/mothers against decapentaplegic (SMAD) proteins. The current study aims to explore the regulation of TGF-β/SMAD signaling by selenophosphate synthetase 1 (SEPHS1). METHODS: Immunohistochemistry was used to detect the expression of SEPHS1 in HCC and adjacent liver tissues. Western blotting and quantitative reverse-transcription PCR were used to detect the protein and mRNA levels in HCC cell lines. Cell migration and invasion were determined by transwell assay. Bioinformatic analysis was conducted to determine SEPHS1 expression in HCC and its correlation with the survival of HCCpatients. RESULTS: Here we report that SEPHS1 is a positive regulator of SMAD proteins. SEPHS1 expression is up-regulated in HCC compared with adjacent liver tissues. SEPHS1 knockdown leads to decreased expression of SMAD2/3/4 and mesenchymal markers including snail, slug and N-cadherin in HCC cells. Furthermore, SEPHS1 knockdown results in a decrease in HCC cells migration and invasion, and suppresses the stimulation of HCC cells migration and invasion by TGF-β. Overexpression of SEPHS1 in HCC cells promotes cell invasion, which can be abrogated by SMAD3 knockdown. Lastly, higher expression of SEPHS1 is correlated with poor prognosis in HCCpatients, as manifested by decreased overall survival and disease-free survival. CONCLUSIONS:SEPHS1 is a positive regulator of TGF-β/SMAD signaling that is up-regulated in HCC. Increased SEPHS1 expression may indicate poor prognosis for patients with HCC.
Authors: Kumardeep Chaudhary; Olivier B Poirion; Liangqun Lu; Sijia Huang; Travers Ching; Lana X Garmire Journal: Clin Cancer Res Date: 2018-09-21 Impact factor: 12.531