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MicroRNA-1277 Inhibits Proliferation and Migration of Hepatocellular Carcinoma HepG2 Cells by Targeting and Suppressing BMP4 Expression and Reflects the Significant Indicative Role in Hepatocellular Carcinoma Pathology and Diagnosis After Magnetic Resonance Imaging Assessment
Authors:Xinshan Cao  Ling Xu  Quanyuan Liu  Lijuan Yang  Na Li  Xiaoxiao Li
Affiliation:* Department of Radiology, Binzhou Medical University Hospital, Binzhou, Shandong, P.R. China† Department of Liver Disease Center, Traditional Chinese Medicine Hospital of Binzhou City, Binzhou, Shandong, P.R. China‡ Department of Experiment Center of Tumor, Binzhou Medical University Hospital, Binzhou, Shandong, P.R. China§ Department of Clinical Laboratory, Binzhou Medical University Hospital, Binzhou, Shandong, P.R. China
Abstract:Our study aimed to investigate the roles and possible regulatory mechanism of miR-1277 in the development of hepatocellular carcinoma (HCC). HCC patients were identified from patients who were diagnosed with focal liver lesions using magnetic resonance imaging (MRI). The expression levels of miR-1277 in the serum of HCC patients and HepG2 cells were measured. Then miR-1277 mimic, miR-1277 inhibitor, or scramble RNA was transfected into HepG2 cells. The effects of miR-1277 overexpression and suppression on HepG2 cell proliferation, migration, and invasion were then investigated. Additionally, the expression levels of epithelial–mesenchymal transition (EMT)-related markers, including E-cadherin, -catenin, and vimentin, were detected. Target prediction and luciferase reporter assay were performed to explore the potential target of miR-1277. miR-1277 was significantly downregulated in the serum of HCC patients and HepG2 cells. Suppression of miR-1277 promoted HepG2 cell proliferation, migration, and invasion, whereas overexpression of miR-1277 had opposite effects. In addition, after miR-1277 was suppressed, the expressions of E-cadherin and -catenin were significantly increased, while the expressions of vimentin were markedly decreased. Bone morphogenetic protein 4 (BMP4) was identified as the direct target of miR-1277. Knockdown of BMP4 reversed the effects of miR-1277 suppression on HepG2 cell migration and invasion, as well as the expressions of E-cadherin, -catenin, and vimentin. Our results indicate that downregulation of miR-1277 may promote the migration and invasion of HepG2 cells by targeting BMP4 to induce EMT. Combination of MRI and miR-1277 level will facilitate the diagnosis and treatment of HCC.
Keywords:Hepatocellular carcinoma (HCC)  Bone morphogenetic protein 4 (BMP4)  miR-1277  Magnetic resonance imaging (MRI)
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