MicroRNA-18a is elevated in prostate cancer and promotes tumorigenesis through suppressing STK4 in vitro and in vivo

T. I. Hsu, C. H. Hsu, K. H. Lee, J. T. Lin, C. S. Chen, K. C. Chang, C. Y J Su, M. Hsiao, P. J. Lu

Research output: Contribution to journalArticle

48 Citations (Scopus)

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) 30 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.

Original languageEnglish
Article numbere99
JournalOncogenesis
Volume3
Issue number4
DOIs
Publication statusPublished - Jan 1 2014

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Protein-Serine-Threonine Kinases
MicroRNAs
Prostatic Neoplasms
Carcinogenesis
Neoplasms
Untranslated Regions
Cell Line
Untranslated RNA
Growth
In Vitro Techniques
Computational Biology
Luciferases
Oncogenes
Nude Mice
Prostate
Seeds
Up-Regulation
Binding Sites
Apoptosis

Keywords

  • miR-18a
  • prostate cancer
  • STK4

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

MicroRNA-18a is elevated in prostate cancer and promotes tumorigenesis through suppressing STK4 in vitro and in vivo. / Hsu, T. I.; Hsu, C. H.; Lee, K. H.; Lin, J. T.; Chen, C. S.; Chang, K. C.; Su, C. Y J; Hsiao, M.; Lu, P. J.

In: Oncogenesis, Vol. 3, No. 4, e99, 01.01.2014.

Research output: Contribution to journalArticle

Hsu, T. I. ; Hsu, C. H. ; Lee, K. H. ; Lin, J. T. ; Chen, C. S. ; Chang, K. C. ; Su, C. Y J ; Hsiao, M. ; Lu, P. J. / MicroRNA-18a is elevated in prostate cancer and promotes tumorigenesis through suppressing STK4 in vitro and in vivo. In: Oncogenesis. 2014 ; Vol. 3, No. 4.
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