Yuan Wang1, Fuquan Chen1, Man Zhao1, Zhe Yang1, Shuqin Zhang1, Lihong Ye2, Hongwei Gao3, Xiaodong Zhang4. 1. State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China. 2. State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, China. 3. Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China. Electronic address: gaohongw369@163.com. 4. State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address: zhangxd@nankai.edu.cn.
Abstract
BACKGROUND AND AIM: Aberrant expression of miR-107 is involved in the development of several human cancers. However, the role of miR-107 in hepatocellular carcinoma (HCC) is not well documented. In the present study, we aim to explore the function of miR-107 in hepatocarcinogenesis. METHODS: Bioinformatics analysis was applied to predict the target genes of miR-107. Luciferase reporter gene assay was performed to verify the miR-107 binding sites in 3'-untranslated region (3'UTR) of high mobility group A2 (HMGA2) mRNA. The expression levels of mRNA and protein were examined using qRT-PCR and Western blot analysis. Functionally, MTT and EdU assays were carried out for proliferation analysis. Clinically, thirty HCC samples and their corresponding peritumor liver tissues were collected. RESULTS: Bioinformatics analysis revealed that miR-107 might target HMGA2 mRNA 3'UTR. Luciferase reporter gene assays verified that the miR-107 binding site was located in the 3'UTR of HMGA2 mRNA. Furthermore, miR-107 could down-regulate HMGA2 at the levels of mRNA and protein in a dose-dependent manner. Interestingly, miR-107 inhibited the proliferation of hepatoma cells, while anti-miR-107 could promote the cell proliferation, which was blocked by the interference of HMGA2. Clinically, miR-107 was lower in HCC samples relative to peritumor liver tissues. The expression levels of miR-107 were negatively correlated with those of HMGA2 mRNA in HCC samples. CONCLUSION: MiR-107 suppresses the proliferation of hepatoma cells by targeting HMGA2 mRNA. Our finding provides new insights into the mechanism of hepatocarcinogenesis.
BACKGROUND AND AIM: Aberrant expression of miR-107 is involved in the development of several humancancers. However, the role of miR-107 in hepatocellular carcinoma (HCC) is not well documented. In the present study, we aim to explore the function of miR-107 in hepatocarcinogenesis. METHODS: Bioinformatics analysis was applied to predict the target genes of miR-107. Luciferase reporter gene assay was performed to verify the miR-107 binding sites in 3'-untranslated region (3'UTR) of high mobility group A2 (HMGA2) mRNA. The expression levels of mRNA and protein were examined using qRT-PCR and Western blot analysis. Functionally, MTT and EdU assays were carried out for proliferation analysis. Clinically, thirty HCC samples and their corresponding peritumor liver tissues were collected. RESULTS: Bioinformatics analysis revealed that miR-107 might target HMGA2 mRNA 3'UTR. Luciferase reporter gene assays verified that the miR-107 binding site was located in the 3'UTR of HMGA2 mRNA. Furthermore, miR-107 could down-regulate HMGA2 at the levels of mRNA and protein in a dose-dependent manner. Interestingly, miR-107 inhibited the proliferation of hepatoma cells, while anti-miR-107 could promote the cell proliferation, which was blocked by the interference of HMGA2. Clinically, miR-107 was lower in HCC samples relative to peritumor liver tissues. The expression levels of miR-107 were negatively correlated with those of HMGA2 mRNA in HCC samples. CONCLUSION:MiR-107 suppresses the proliferation of hepatoma cells by targeting HMGA2 mRNA. Our finding provides new insights into the mechanism of hepatocarcinogenesis.
Authors: Sanchari Roy; Guido J Hooiveld; Marco Seehawer; Stefano Caruso; Florian Heinzmann; Anne T Schneider; Anna K Frank; David Vargas Cardenas; Roland Sonntag; Mark Luedde; Christian Trautwein; Ilan Stein; Eli Pikarsky; Sven Loosen; Frank Tacke; Marc Ringelhan; Seda Kilinc Avsaroglu; Andrei Goga; Marie-Annick Buendia; Mihael Vucur; Mathias Heikenwalder; Jessica Zucman-Rossi; Lars Zender; Christoph Roderburg; Tom Luedde Journal: Gastroenterology Date: 2018-08-27 Impact factor: 22.682