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Involvement of microRNA-718, a new regulator of EGR3, in regulation of malignant phenotype of HCC cells |
Zhong-dong Wang, Fan-yong Qu, Yuan-yuan Chen, Zhang-shen Ran, Hai-yan Liu, Hai-dong Zhang |
Clinical Laboratory of Taishan Sanatorium of Shandong Province, Tai'an 271001, China; Interventional Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai 264100, China; Center of Health Examination, Affiliated Hospital of Taishan Medical University, Tai'an 271001, China; Department of Oncology, Affiliated Hospital of Taishan Medical University, Tai'an 271001, China; Department of Basic Medicine, Taishan Medical University, Tai'an 271001, China |
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Abstract Objective: Hepatocellular carcinoma (HCC) is still one of the most common death-related malignancies worldwide. Because the way onset and progression are hidden most, HCC diagnoses are made at an advanced stage, when they are unsuitable for surgical resection. MicroRNAs are a class of small non-coding RNAs, participating in many aspects of cancers. In this study, we tried to establish the role of microRNA-718 (miR-718) in the malignant phenotype of HCC cells and its possible role in HCC diagnosis. Methods: Here we first used a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, Transwell migration and invasion assays, and colony formation assay to evaluate the impact of miR-718 on the malignant phenotypes of HCC cells. Then, we used bioinformatic methods to predict the target gene of miR-718 and used green fluorescence protein (GFP) reporter assay, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) to validate the regulation relationship. Finally, we determined the role of the target gene in the HCC phenotype. Results: We found that the expression of miR-718 was significantly reduced in various HCC cell lines and HCC tissues. Re-expression of miR-718 significantly reduced the cellular viability and colony formation ability as well as inhibited the migration and invasion abilities of HCC cell lines. Early growth response protein 3 (EGR3) is a direct target of miR-718 and is negatively regulated by miR-718. EGR3 could increase the viability and proliferation of HCC cells, and promot the migration and invasion of HCC cells. Conclusions: miR-718 acts as a tumor suppressive microRNA in HCC via regulating the expression of EGR3, which may provide a new diagnostic marker and treatment target for HCC.
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Received: 10 May 2016
Published: 03 January 2017
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