title: miR-451 inhibits cell proliferation in human hepatocellular carcinoma through direct suppression of IKK-β.
abstract: It has been demonstrated that nuclear factor-kappa B (NF-κB), which is overactivated in hepatocellular carcinoma (HCC), plays important roles in the development of HCC. Recently, a group of dysregulated micro RNAs were reported to be involved in HCC progression. Further understanding of micro RNA-mediated regulation of NF-κB pathway may provide novel therapeutic targets for HCC. In this study, we found that miR-451 expression was markedly downregulated in HCC cells and tissues compared with immortalized normal liver epithelial cells and adjacent non- cancerous tissues, respectively. Upregulation of miR-451 inhibited, while downregulation of miR-451 promoted, the tumorigenicity of HCC cells both in vitro and in vivo. These changes in the properties of HCC cells were associated with deregulation of two well-known cellular G1/S transitional regulators, cyclin D1 and c-Myc, which are downstream targets of NF-κB pathway. Furthermore, we demonstrated that miR-451 upregulation led to downregulation of cyclin D1 and c-Myc through inhibition of NF-κB pathway initiated by direct targeting of the IKBKB 3'-untranslated region. Therefore, these results suggest that miR-451 downregulation plays an important role in promoting proliferation of HCC cells and may provide the basis for the development of novel anti-HCC therapies.
authors.affiliation: Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Li
authors.forename: Xian-Cheng
authors.initials: XC
authors.lastname: Zeng
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Jian-Ting
authors.initials: JT
authors.lastname: Long
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Tan
authors.forename: Wei-Xia
authors.initials: WX
authors.lastname: Zeng
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C531201:MIRN451 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019938:Cyclin D1; D051550:I-kappa B Kinase