title: MicroRNA-18a is elevated in prostate cancer and promotes tumorigenesis through suppressing STK4 in vitro and in vivo.
abstract: MicroRNAs (miRNAs) comprise a class of short, non-coding RNAs that regulate protein synthesis through posttranscriptional modifications. In this study, we found significant upregulation of miR-18a in prostate cancer specimens and prostate cancer cell lines compared with the normal controls. MiRNAs can be separated into two groups based on whether they regulate tumor suppressors or oncogenes. In our previous study, we found that miR-18a, which belongs to the miR17-92 cluster, is upregulated in prostate cancer; the objective of this study was to investigate the associated regulatory mechanisms. We found that miR-18a is upregulated in clinical tumor specimens and cancer cell lines. Our bioinformatics analysis showed that the serine/threonine-protein kinase 4 (STK4) 3' untranslated region contains a highly conserved binding site for the miR-18a seed region. Luciferase reporter assays were performed to indicate that STK4 is a direct target of miR-18a. Interestingly, miR-18a knockdown decreased cell growth in prostate cancer cells and significantly decreased prostate tumor growth in in vivo nude mice experiments through STK4-mediated dephosphorylation of AKT and thereby inducing apoptosis. Our results suggest that miR-18a acts as an oncomiR targeting STK4 in prostate cancer, and inhibition of miR-18a expression may offer therapeutically beneficial option for prostate cancer treatment.
authors.affiliation: Institute of Basic Medical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: T-I
authors.initials: TI
authors.lastname: Hsu
authors.affiliation: Department of Plastic Surgery, Chia-Yi Christian Hospital, Chia-Yi, Taiwan.
authors.forename: C-H
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: K-H
authors.initials: KH
authors.lastname: Lee
authors.affiliation: 1] Institute of Clinical Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan [2] Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: J-T
authors.initials: JT
authors.lastname: Lin
authors.affiliation: 1] Institute of Basic Medical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan [2] Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: C-S
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: K-C
authors.initials: KC
authors.lastname: Chang
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: C-Yj
authors.initials: CY
authors.lastname: Su
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: M
authors.initials: M
authors.lastname: Hsiao
authors.affiliation: 1] Institute of Basic Medical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan [2] Institute of Clinical Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: P-J
authors.initials: PJ
authors.lastname: Lu
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