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Published in: Journal of Cancer Research and Clinical Oncology 11/2017

01-11-2017 | Original Article – Cancer Research

Induction of alpha-methylacyl-CoA racemase by miR-138 via up-regulation of β-catenin in prostate cancer cells

Authors: Kati Erdmann, Knut Kaulke, Christiane Rieger, Manfred P. Wirth, Susanne Fuessel

Published in: Journal of Cancer Research and Clinical Oncology | Issue 11/2017

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Abstract

Purpose

Alpha-methylacyl-CoA racemase (AMACR) is highly overexpressed in prostate cancer (PCa) and its transcriptional regulators include various transcription factors and CTNNB1/β-catenin. Our previous findings suggested a post-transcriptional regulation by the tumor-suppressive microRNA miR-138 in PCa. Thus, the aim of this study was to demonstrate the direct interaction of miR-138 with the 3′-UTR of AMACR. Furthermore, the influence of miR-138 on the expression of AMACR and selected AMACR regulators was investigated in PCa cells.

Methods

Using DU-145, PC-3, and LNCaP PCa cells, the effect of exogenous miR-138 on AMACR and selected AMACR regulators was determined by quantitative PCR and Western blot. Luciferase reporter assays were used to verify target and promoter interaction.

Results

Using a luciferase reporter assay a direct interaction of miR-138 with the AMACR-3′-UTR was confirmed. Surprisingly, AMACR expression was up-regulated by up to 125% by exogenous miR-138 in PCa cells. The lack of any miR-138 binding sites within the AMACR promoter suggested an indirect mechanism of up-regulation. Therefore, the effect of miR-138 on selected AMACR regulators including CTNNB1/β-catenin, RELA, SMAD4, SP1, and TCF4 was evaluated. MiR-138 solely evoked an up-regulation of CTNNB1 mRNA expression and β-catenin protein levels by up to 75%. Further in silico analysis revealed a binding site for miR-138 within the CTNNB1 promoter. MiR-138 could enhance the activity of the CTNNB1 promoter, which in turn could contribute to the observed AMACR up-regulation.

Conclusions

The present findings suggest that miR-138 can indirectly up-regulate AMACR via transcriptional induction of CTNNB1, at least in vitro in PCa cells.
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Metadata
Title
Induction of alpha-methylacyl-CoA racemase by miR-138 via up-regulation of β-catenin in prostate cancer cells
Authors
Kati Erdmann
Knut Kaulke
Christiane Rieger
Manfred P. Wirth
Susanne Fuessel
Publication date
01-11-2017
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 11/2017
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-017-2484-5

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