Xiao Hu1, Yujie Feng1, Lin Sun2, Linlin Qu1, Chuandong Sun3. 1. Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, China. 2. Department of ICU, The Affiliated Hospital of Qingdao University, Qingdao, China. 3. Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, China. sunchuandong@hotmail.com.
Abstract
BACKGROUND: Aberrant expression of microRNAs contributes to tumor growth and progression. AIMS: This study was designed to explore the prognostic and biological significance of miR-330 in hepatocellular carcinoma (HCC). METHODS: The expression of miR-330 and its associations with tumor parameters and overall survival were analyzed in HCC patients. The biological functions of miR-330 in HCC cell growth, invasion, and tumorigenesis were investigated. Bioinformatic analysis and luciferase reporter assays were performed to search for potential targets of miR-330. RESULTS: The miR-330 level was significantly higher in HCCs than in adjacent normal tissues (P = 0.0085). High expression of miR-330 was significantly associated with more aggressive phenotypes and shorter overall survival in HCC. Loss- and gain-of-function studies indicated the favorable effect of miR-330 on tumor cell growth, invasion, and tumorigenesis. Inhibitor of growth 4 (ING4) was identified to be a direct target of miR-330. Overexpression of miR-330 reduced the expression of ING4 in HCC cells. Importantly, restoration of ING4 almost completely reversed the promotion of HCC cell proliferation and invasion by miR-330. CONCLUSIONS: Altogether, this study demonstrates that upregulation of miR-330 is associated with poor prognosis and contributes to more aggressive phenotypes of HCC. The oncogenic role of miR-330 in HCC is linked to downregulation of ING4.
BACKGROUND: Aberrant expression of microRNAs contributes to tumor growth and progression. AIMS: This study was designed to explore the prognostic and biological significance of miR-330 in hepatocellular carcinoma (HCC). METHODS: The expression of miR-330 and its associations with tumor parameters and overall survival were analyzed in HCC patients. The biological functions of miR-330 in HCC cell growth, invasion, and tumorigenesis were investigated. Bioinformatic analysis and luciferase reporter assays were performed to search for potential targets of miR-330. RESULTS: The miR-330 level was significantly higher in HCCs than in adjacent normal tissues (P = 0.0085). High expression of miR-330 was significantly associated with more aggressive phenotypes and shorter overall survival in HCC. Loss- and gain-of-function studies indicated the favorable effect of miR-330 on tumor cell growth, invasion, and tumorigenesis. Inhibitor of growth 4 (ING4) was identified to be a direct target of miR-330. Overexpression of miR-330 reduced the expression of ING4 in HCC cells. Importantly, restoration of ING4 almost completely reversed the promotion of HCC cell proliferation and invasion by miR-330. CONCLUSIONS: Altogether, this study demonstrates that upregulation of miR-330 is associated with poor prognosis and contributes to more aggressive phenotypes of HCC. The oncogenic role of miR-330 in HCC is linked to downregulation of ING4.
Authors: Ruba Al-Abdulla; Elisa Lozano; Rocio I R Macias; Maria J Monte; Oscar Briz; Colm J O'Rourke; Maria A Serrano; Jesus M Banales; Matias A Avila; Maria L Martinez-Chantar; Andreas Geier; Jesper B Andersen; Jose J G Marin Journal: Br J Pharmacol Date: 2019-02-11 Impact factor: 8.739