title: HBx elevates oncoprotein AEG-1 expression to promote cell migration by downregulating miR-375 and miR-136 in malignant hepatocytes.
abstract: The hepatitis B viral X protein (HBx) has been established to implicate in the development of HBV-related hepatocellular carcinoma (HCC) via multiple pathways. The oncoprotein astrocyte elevated gene-1 (AEG-1) is overexpressed in various tumors, including HCC, and plays critical roles in promoting cell migration and invasion. However, the mechanisms for AEG-1 upregulation in tumors are largely unknown. In this study, we found that HBx could elevate AEG-1 protein level without altering its mRNA level. When blocking AEG-1 expression with siRNA in HBx-transfected cells, the HBx-induced cell migration was significantly suppressed. Further study indicated that miR-375 and miR-136 that targeted AEG-1 were downregulated with HBx expression. Overexpressing miR-375 and miR-136 could effectively attenuate HBx-mediated AEG-1 elevation and cell migration. These results demonstrated that HBx enabled to increase oncoprotein AEG-1 expression to promote cell migration via downregulating miR-375 and miR-136. Our findings provide a novel insight into AEG-1 upregulation in HCC and shed new light on HBx promoting HCC progression. Meanwhile, our results also suggest that miR-375 and miR-136 may have the miRNA-based therapeutic potential in HBV-associated HCC.
authors: 1 Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University , Shanghai, China .
authors: Jing
authors: J
authors: Zhao
authors: Wenjie
authors: W
authors: Wang
authors: Yuxian
authors: Y
authors: Huang
authors: Jing
authors: J
authors: Wu
authors: Mingquan
authors: M
authors: Chen
authors: Peng
authors: P
authors: Cui
authors: Wenhong
authors: W
authors: Zhang
authors: Ying
authors: Y
authors: Zhang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000821:virology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D008565:Membrane Proteins; D035683:MicroRNAs / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D015534:Trans-Activators / Q000096:biosynthesis / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D015815:Cell Adhesion Molecules; C577037:MIRN136 microRNA, human; C540933:MIRN375 microRNA, human; C483039:MTDH protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein