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MiR-210 expression in tumor tissue and in vitro effects of its silencing in renal cell carcinoma

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Tumor Biology

Abstract

Renal cell carcinoma (RCC) is the most common neoplasm of adult kidney accounting for about 3 % of adult malignancies. MicroRNAs (miRNAs) are a class of naturally occurring, short non-coding RNAs that regulate gene expression at the post-transcriptional level. We determined global miRNA expression profiles of RCC and parallel renal parenchyma tissues by using quantitative reverse transcriptase-polymerase chain reaction-based TaqMan low-density arrays. Afterward, we validated the difference in miR-210 expression levels on the larger group of RCC patients (35 RCC versus 10 non-tumorous parenchyma samples). Functional in vitro experiments were performed on ACHN and CAKI-2 RCC cell lines transfected with miRNA-210 inhibitor. Cell viability, apoptosis, cell cycle, scratch wound migration assay, and invasion assay (xCELLigence) were performed. We have identified original ccRCC-specific miRNA signature in clinical samples (73 miRNAs were significantly downregulated and five miRNAs upregulated (P < 0.003)). Increased expression levels of miR-210 in RCC tumor tissue were independently validated. We observed decreased viability of ACHN and CAKI-2 cells and accumulation of CAKI-2 in G2 phase of cell cycle after silencing of miR-210 expression. Downregulation of miR-210 also reduced the migratory and invasive potential of ACHN metastatic RCC cells. Moreover, we showed downregulation of HIF1a protein in both cell lines after miR-210 silencing indicating participation of miR-210 in hypoxic processes of RCC not only through regulation of its target mRNAs but also by indirect regulation of HIF1a. To our knowledge, this is the first report to show miR-210 regulatory effects on cell migration, invasive potential, and HIF1a protein in RCC cells.

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Acknowledgment

This work was supported by grant IGA NT/13547 of the Czech Ministry of Health, by Institutional Resources for Supporting the Research Organization provided by the Czech Ministry of Health in 2012 to Masaryk Memorial Cancer Institute, by The Ministry of Education, Youth and Sports for the project BBMRI CZ (LM2010004), and by the project “CEITEC–Central European Institute of Technology” (CZ.1.05/1.1.00/02.0068).

Conflicts of interest

None.

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Authors and Affiliations

  1. Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53, Brno, Czech Republic

    Martina Redova, Alexandr Poprach, Radek Lakomy, Marek Svoboda, Rostislav Vyzula & Ondrej Slaby

  2. Department of Oncourology, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic

    Jan Dolezel

  3. Central European Institute of Technology, Masaryk University, Kamenice 5, Brno, Czech Republic

    Martina Redova, Andrej Besse, Robert Iliev & Ondrej Slaby

  4. Institute of Clinical Biochemistry and Diagnostics, Faculty of Medicine and Faculty Hospital in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic

    Jana Nekvindova

  5. Laboratory of Experimental Medicine, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and Palacky University affiliated Hospital Olomouc, Brno, Czech Republic

    Lenka Radova

Authors
  1. Martina Redova
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  2. Alexandr Poprach
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  3. Andrej Besse
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  4. Robert Iliev
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  9. Jan Dolezel
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  10. Rostislav Vyzula
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  11. Ondrej Slaby
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Corresponding author

Correspondence to Ondrej Slaby.

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Martina Redova and Alexandr Poprach contributed equally to this work.

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Redova, M., Poprach, A., Besse, A. et al. MiR-210 expression in tumor tissue and in vitro effects of its silencing in renal cell carcinoma. Tumor Biol. 34, 481–491 (2013). https://doi.org/10.1007/s13277-012-0573-2

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  • DOI: https://doi.org/10.1007/s13277-012-0573-2

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