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.

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

Zobrazit více v PubMed

Methods Mol Biol. 2011;676:3-22 PubMed

Cell Cycle. 2010 Mar 15;9(6):1072-83 PubMed

J Cancer. 2011;2:515-26 PubMed

Cancer Lett. 2011 Nov 28;310(2):160-9 PubMed

Oncogene. 2007 Jun 14;26(28):4148-57 PubMed

World J Urol. 2011 Jun;29(3):367-73 PubMed

Nat Rev Genet. 2009 Oct;10(10):704-14 PubMed

Breast Cancer Res. 2009;11(3):R27 PubMed

Cancer Biol Ther. 2008 Feb;7(2):255-64 PubMed

Eur J Surg Oncol. 2009 Oct;35(10):1119-23 PubMed

Mol Cell Biol. 2011 Jul;31(13):2696-706 PubMed

Cancer Res. 2007 Feb 1;67(3):976-83 PubMed

Clin Biochem. 2010 Jan;43(1-2):150-8 PubMed

Cell. 2009 Feb 20;136(4):642-55 PubMed

Methods Enzymol. 2006;411:119-34 PubMed

Mol Cancer. 2009 Nov 14;8:102 PubMed

BMC Med. 2010 Oct 21;8:65 PubMed

J Exp Clin Cancer Res. 2010 Jul 07;29:90 PubMed

Biochem Biophys Res Commun. 2011 Feb 11;405(2):153-6 PubMed

J Biol Chem. 2008 Jun 6;283(23):15878-83 PubMed

Cell Cycle. 2009 Sep 1;8(17):2756-68 PubMed

PLoS One. 2011;6(6):e20980 PubMed

J Pathol. 2008 Dec;216(4):418-27 PubMed

PLoS One. 2010 Dec 30;5(12):e15224 PubMed

J Urol. 2011 Sep;186(3):1077-83 PubMed

J Proteome Res. 2011 Jan 7;10(1):191-9 PubMed

J Pathol. 2011 Jun;224(2):280-8 PubMed

Clin Sci (Lond). 2011 Mar;120(5):183-93 PubMed

J Lipid Res. 2010 Aug;51(8):2223-33 PubMed

MiR-205 functions as a tumor suppressor in adenocarcinoma and an oncogene in squamous cell carcinoma of esophagus

Combination of MiR-378 and MiR-210 Serum Levels Enables Sensitive Detection of Renal Cell Carcinoma

Diagnostic and prognostic potential of miR-21, miR-29c, miR-148 and miR-203 in adenocarcinoma and squamous cell carcinoma of esophagus