title: miR-106b-25/miR-17-92 clusters: polycistrons with oncogenic roles in hepatocellular carcinoma.
abstract: MicroRNAs are small endogenously expressed RNA molecules which are involved in the process of silencing gene expression through translational regulation. The polycistronic miR-17-92 cluster is the first microRNA cluster shown to play a role in tumorigenesis. It has two other paralogs in the human genome, the miR-106b-25 cluster and the miR-106a-363 cluster. Collectively, the microRNAs encoded by these clusters can be further grouped based on the seed sequences into four families, namely the miR-17, the miR-92, the miR-18 and the miR-19 families. Over-expression of the miR-106b-25 and miR-17-92 clusters has been reported not only during the development of cirrhosis but also subsequently during the development of hepatocellular carcinoma. Members of these clusters have also been shown to affect the replication of hepatitis B and hepatitis C viruses. Various targets of these microRNAs have been identified, and these targets are involved in tumor growth, cell survival and metastasis. In this review, we first describe the regulation of these clusters by c-Myc and E2F1, and how the members of these clusters in turn regulate E2F1 expression forming an auto-regulatory loop. In addition, the roles of the various members of the clusters in affecting relevant target gene expression in the pathogenesis of hepatocellular carcinoma will also be discussed.
authors.affiliation: Weiqi Tan, Theresa MC Tan, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore S117597, Singapore.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Tan
authors.affiliation: Weiqi Tan, Theresa MC Tan, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore S117597, Singapore.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Weiqi Tan, Theresa MC Tan, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore S117597, Singapore.
authors.forename: Seng-Gee
authors.initials: SG
authors.lastname: Lim
authors.affiliation: Weiqi Tan, Theresa MC Tan, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore S117597, Singapore.
authors.forename: Theresa M C
authors.initials: TM
authors.lastname: Tan
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002470:Cell Survival; D050687:E2F1 Transcription Factor / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D064168:Minichromosome Maintenance Complex Component 7 / Q000378:metabolism; D005810:Multigene Family; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D062085:RNA, Long Noncoding; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction
chemical_list: D050687:E2F1 Transcription Factor; C568997:MIR17HG, human; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C101624:MCM7 protein, human; D064168:Minichromosome Maintenance Complex Component 7
keywords: Hepatocellular carcinoma; Liver cirrhosis; MicroRNAs; miR-106b-25 cluster; miR-17-92 cluster