title: Downregulation of microRNA miR-520h by E1A contributes to anticancer activity.
abstract: The leading cause of death in cancer patients is cancer metastasis, for which there is no effective treatment. MicroRNAs (miRNA) have been shown to play a significant role in cancer metastasis through regulation of gene expression. The adenovirus type 5 E1A (E1A) is associated with multiple tumor-suppressing activities including the inhibition of metastasis, and E1A gene therapies have been tested in several clinical trials. However, the mechanisms involved in E1A-mediated tumor-suppressing activities are not yet completely defined. Here, we showed that E1A downregulated the expression of the miRNA miR-520h, which was critical for E1A-mediated cancer cell mobility and in vitro invasion activity. In addition, we identified a signal cascade, namely, E1A-->miRNA-520h-->PP2A/C-->IkappaB kinase-->NF-kappaB-->Twist, in which E1A inhibited the expression of Twist through downregulation of miR-520h and the signal cascade. Our results indicated a functional link between miR-520h and tumorigenicity/invasive ability and provided a new insight into the role of E1A-mediated miRNA regulation in tumor suppression. Therefore, the results identified a new cascade of E1A-mediated tumor suppression activity via downregulation of miRNA-520h expression.
authors.affiliation: Graduate Institute of Cancer Biology, College of Medicine, China Medical University and Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Jen-Liang
authors.initials: JL
authors.lastname: Su
authors.forename: Poshen B
authors.initials: PB
authors.lastname: Chen
authors.forename: Ya-Huey
authors.initials: YH
authors.lastname: Chen
authors.forename: Shang-Chih
authors.initials: SC
authors.lastname: Chen
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Chang
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Jan
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Cheng
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D015536:Down-Regulation; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D017500:Adenovirus E1A Proteins; D000970:Antineoplastic Agents; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D051879:Twist-Related Protein 1; D054648:Protein Phosphatase 2