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Published in: BMC Medicine 1/2010

Open Access 01-12-2010 | Commentary

MicroRNAs: exploring a new dimension in the pathogenesis of kidney cancer

Authors: Nicole MA White, George M Yousef

Published in: BMC Medicine | Issue 1/2010

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Abstract

Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. The role of the von-Hippel-Lindeau (VHL) tumour suppressor gene is well established in RCC with a loss of VHL protein leading to accumulated hypoxia-induced factor (HIF) and the subsequent transcriptional activation of multiple downstream targets. Recently, microRNAs (miRNAs) have been shown to be differentially expressed in RCC and their role in RCC pathogenesis is emerging. This month, in BMC Medicine, Gleadle and colleagues show that certain miRNAs are regulated by VHL in either a hypoxia-inducible factor (HIF)-dependent or HIF-independent manner in RCC. They also show that miRNA expression correlates with the survival of RCC patients.
In this commentary, we discuss the current understanding of the role of miRNAs in RCC and the different possible scenarios of their involvement in RCC pathogenesis. We also address their clinical significance as tumour markers, together with the potential use of miRNAs as therapeutic targets. Finally, we discuss some of the challenges that face the fast-evolving field of miRNAs, including the identification and validation of miRNA targets and the difficulties associated with establishing a link between miRNA expression and biological effects. A more thorough understanding of the biological nature of miRNAs and careful experimental planning will help us to reveal the complex role that miRNAs play in RCC pathogenesis.
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Literature
1.
go back to reference Neal CS, Michael MZ, Rawlings LH, Van der Hoek MB, Gleadle JM: The VHL-dependent regulation of microRNAs in renal cell cancer. BMC Med. 2010, 8: 64-10.1186/1741-7015-8-64.CrossRefPubMedPubMedCentral Neal CS, Michael MZ, Rawlings LH, Van der Hoek MB, Gleadle JM: The VHL-dependent regulation of microRNAs in renal cell cancer. BMC Med. 2010, 8: 64-10.1186/1741-7015-8-64.CrossRefPubMedPubMedCentral
2.
go back to reference Turner KJ, Moore JW, Jones A, Taylor CF, Cuthbert-Heavens D, Han C, Leek RD, Gatter KC, Maxwell PH, Ratcliffe PJ, et al: Expression of hypoxia-inducible factors in human renal cancer: relationship to angiogenesis and to the von Hippel-Lindau gene mutation. Cancer Res. 2002, 62: 2957-2961.PubMed Turner KJ, Moore JW, Jones A, Taylor CF, Cuthbert-Heavens D, Han C, Leek RD, Gatter KC, Maxwell PH, Ratcliffe PJ, et al: Expression of hypoxia-inducible factors in human renal cancer: relationship to angiogenesis and to the von Hippel-Lindau gene mutation. Cancer Res. 2002, 62: 2957-2961.PubMed
3.
go back to reference Young AP, Schlisio S, Minamishima YA, Zhang Q, Li L, Grisanzio C, Signoretti S, Kaelin WG: VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400. Nat Cell Biol. 2008, 10: 361-369. 10.1038/ncb1699.CrossRefPubMed Young AP, Schlisio S, Minamishima YA, Zhang Q, Li L, Grisanzio C, Signoretti S, Kaelin WG: VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400. Nat Cell Biol. 2008, 10: 361-369. 10.1038/ncb1699.CrossRefPubMed
4.
go back to reference Krol J, Loedige I, Filipowicz W: The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010, 11: 597-610.PubMed Krol J, Loedige I, Filipowicz W: The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010, 11: 597-610.PubMed
5.
go back to reference He L, Hannon GJ: MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004, 5: 522-531. 10.1038/nrg1379.CrossRefPubMed He L, Hannon GJ: MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004, 5: 522-531. 10.1038/nrg1379.CrossRefPubMed
6.
7.
go back to reference Lewis BP, Burge CB, Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005, 120: 15-20. 10.1016/j.cell.2004.12.035.CrossRefPubMed Lewis BP, Burge CB, Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005, 120: 15-20. 10.1016/j.cell.2004.12.035.CrossRefPubMed
8.
go back to reference Chow TF, Youssef YM, lianidou E, Romaschin AD, Honey RJ, Stewart R, Pace KT, Yousef GM: Differential expression profiling of microRNAs and their potential involvement in renal cell carcinoma pathogenesis. Clin Biochem. 2009, 43: 150-158. 10.1016/j.clinbiochem.2009.07.020.CrossRefPubMed Chow TF, Youssef YM, lianidou E, Romaschin AD, Honey RJ, Stewart R, Pace KT, Yousef GM: Differential expression profiling of microRNAs and their potential involvement in renal cell carcinoma pathogenesis. Clin Biochem. 2009, 43: 150-158. 10.1016/j.clinbiochem.2009.07.020.CrossRefPubMed
9.
go back to reference Schaefer A, Jung M, Kristiansen G, Lein M, Schrader M, Miller K, Stephan C, Jung K: MicroRNAs and cancer: current state and future perspectives in urologic oncology. Urol Oncol. 2010, 28: 4-13.CrossRefPubMed Schaefer A, Jung M, Kristiansen G, Lein M, Schrader M, Miller K, Stephan C, Jung K: MicroRNAs and cancer: current state and future perspectives in urologic oncology. Urol Oncol. 2010, 28: 4-13.CrossRefPubMed
10.
go back to reference White NM, Bao TT, Grigull J, Youssef YM, Girgis A, Diamandis M, Fatoohi E, Metias M, Honey RJ, Stewart R, et al: MiRNA profiling in clear cell renal cell carcinoma: biomarker discovery and the identification of potential controls and consequences of miRNA dysregulation. J Path. 2010, in press White NM, Bao TT, Grigull J, Youssef YM, Girgis A, Diamandis M, Fatoohi E, Metias M, Honey RJ, Stewart R, et al: MiRNA profiling in clear cell renal cell carcinoma: biomarker discovery and the identification of potential controls and consequences of miRNA dysregulation. J Path. 2010, in press
11.
go back to reference White NM, Fatoohi E, Metias M, Jung K, Stephan C, Yousef GM: Metastamirs: A stepping stone towards improved cancer management. Nature Rev Clin Oncol. 2010, in press White NM, Fatoohi E, Metias M, Jung K, Stephan C, Yousef GM: Metastamirs: A stepping stone towards improved cancer management. Nature Rev Clin Oncol. 2010, in press
12.
go back to reference Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ, et al: Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007, 26: 745-752. 10.1016/j.molcel.2007.05.010.CrossRefPubMedPubMedCentral Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ, et al: Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007, 26: 745-752. 10.1016/j.molcel.2007.05.010.CrossRefPubMedPubMedCentral
13.
go back to reference Shalgi R, Pilpel Y, Oren M: Repression of transposable-elements - a microRNA anti-cancer defense mechanism?. Trends Genet. 2010, 26: 253-259. 10.1016/j.tig.2010.03.006.CrossRefPubMed Shalgi R, Pilpel Y, Oren M: Repression of transposable-elements - a microRNA anti-cancer defense mechanism?. Trends Genet. 2010, 26: 253-259. 10.1016/j.tig.2010.03.006.CrossRefPubMed
14.
go back to reference Jung M, Mollenkopf HJ, Grimm C, Wagner I, Albrecht M, Waller T, Pilarsky C, Johannsen M, Stephan C, Lehrach H, et al: MicroRNA profiling of clear cell renal cell cancer identifies a robust signature to define renal malignancy. J Cell Mol Med. 2009, 19: 3918-3928. 10.1111/j.1582-4934.2009.00705.x.CrossRef Jung M, Mollenkopf HJ, Grimm C, Wagner I, Albrecht M, Waller T, Pilarsky C, Johannsen M, Stephan C, Lehrach H, et al: MicroRNA profiling of clear cell renal cell cancer identifies a robust signature to define renal malignancy. J Cell Mol Med. 2009, 19: 3918-3928. 10.1111/j.1582-4934.2009.00705.x.CrossRef
15.
go back to reference Chow TF, Mankaruos M, Scorilas A, Youssef Y, Girgis A, Mossad S, Metias S, Rofael Y, Honey RJ, Stewart R, et al: The miR-17-92 cluster is over expressed in, and has an oncogenic effect on, renal cell carcinoma. J Urol. 2010, 183: 743-751. 10.1016/j.juro.2009.09.086.CrossRefPubMed Chow TF, Mankaruos M, Scorilas A, Youssef Y, Girgis A, Mossad S, Metias S, Rofael Y, Honey RJ, Stewart R, et al: The miR-17-92 cluster is over expressed in, and has an oncogenic effect on, renal cell carcinoma. J Urol. 2010, 183: 743-751. 10.1016/j.juro.2009.09.086.CrossRefPubMed
16.
go back to reference Chen Z, Li Y, Zhang H, Huang P, Luthra R: Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene. 2010, 29: 4362-4368. 10.1038/onc.2010.193.CrossRefPubMed Chen Z, Li Y, Zhang H, Huang P, Luthra R: Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene. 2010, 29: 4362-4368. 10.1038/onc.2010.193.CrossRefPubMed
17.
go back to reference Favaro E, Ramachandran A, McCormick R, Gee H, Blancher C, Crosby M, Devlin C, Blick C, Buffa F, Li JL, et al: MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU. PLoS ONE. 2010, 5: e10345-10.1371/journal.pone.0010345.CrossRefPubMedPubMedCentral Favaro E, Ramachandran A, McCormick R, Gee H, Blancher C, Crosby M, Devlin C, Blick C, Buffa F, Li JL, et al: MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU. PLoS ONE. 2010, 5: e10345-10.1371/journal.pone.0010345.CrossRefPubMedPubMedCentral
18.
go back to reference Gonsalves CS, Kalra VK: Hypoxia-mediated expression of 5-lipoxygenase-activating protein involves HIF-1alpha and NF-kappaB and microRNAs 135a and 199a-5p. J Immunol. 2010, 184: 3878-3888. 10.4049/jimmunol.0902594.CrossRefPubMed Gonsalves CS, Kalra VK: Hypoxia-mediated expression of 5-lipoxygenase-activating protein involves HIF-1alpha and NF-kappaB and microRNAs 135a and 199a-5p. J Immunol. 2010, 184: 3878-3888. 10.4049/jimmunol.0902594.CrossRefPubMed
19.
go back to reference Muth M, Theophile K, Hussein K, Jacobi C, Kreipe H, Bock O: Hypoxia-induced down-regulation of microRNA-449a/b impairs control over targeted SERPINE1 (PAI-1) m. J Transl Med. 2010, 8: 33-10.1186/1479-5876-8-33.CrossRefPubMedPubMedCentral Muth M, Theophile K, Hussein K, Jacobi C, Kreipe H, Bock O: Hypoxia-induced down-regulation of microRNA-449a/b impairs control over targeted SERPINE1 (PAI-1) m. J Transl Med. 2010, 8: 33-10.1186/1479-5876-8-33.CrossRefPubMedPubMedCentral
20.
go back to reference Metias SM, lianidou E, Yousef GM: MicroRNAs in clinical oncology: at the crossroads between promises and problems. J Clin Pathol. 2009, 62: 771-776. 10.1136/jcp.2009.064717.CrossRefPubMed Metias SM, lianidou E, Yousef GM: MicroRNAs in clinical oncology: at the crossroads between promises and problems. J Clin Pathol. 2009, 62: 771-776. 10.1136/jcp.2009.064717.CrossRefPubMed
21.
go back to reference Fridman E, Dotan Z, Barshack I, David MB, Dov A, Tabak S, Zion O, Benjamin S, Benjamin H, Kuker H, et al: Accurate molecular classification of renal tumors using MicroRNA expression. J Mol Diagn. 2010, 12: 687-696. 10.2353/jmoldx.2010.090187.CrossRefPubMedPubMedCentral Fridman E, Dotan Z, Barshack I, David MB, Dov A, Tabak S, Zion O, Benjamin S, Benjamin H, Kuker H, et al: Accurate molecular classification of renal tumors using MicroRNA expression. J Mol Diagn. 2010, 12: 687-696. 10.2353/jmoldx.2010.090187.CrossRefPubMedPubMedCentral
22.
go back to reference Arsanious A, Bjarnason GA, Yousef GM: From bench to bedside: current and future applications of molecular profiling in renal cell carcinoma. Mol Cancer. 2009, 8: 20-10.1186/1476-4598-8-20.CrossRefPubMedPubMedCentral Arsanious A, Bjarnason GA, Yousef GM: From bench to bedside: current and future applications of molecular profiling in renal cell carcinoma. Mol Cancer. 2009, 8: 20-10.1186/1476-4598-8-20.CrossRefPubMedPubMedCentral
23.
go back to reference Petillo D, Kort EJ, Anema J, Furge KA, Yang XJ, Teh BT: MicroRNA profiling of human kidney cancer subtypes. Int J Oncol. 2009, 35: 109-114. 10.3892/ijo_00000318.CrossRefPubMed Petillo D, Kort EJ, Anema J, Furge KA, Yang XJ, Teh BT: MicroRNA profiling of human kidney cancer subtypes. Int J Oncol. 2009, 35: 109-114. 10.3892/ijo_00000318.CrossRefPubMed
24.
go back to reference Seto AG: The road toward microRNA therapeutics. Int J Biochem Cell Biol. 2010, 42: 1298-1305. 10.1016/j.biocel.2010.03.003.CrossRefPubMed Seto AG: The road toward microRNA therapeutics. Int J Biochem Cell Biol. 2010, 42: 1298-1305. 10.1016/j.biocel.2010.03.003.CrossRefPubMed
25.
go back to reference Petrocca F, Lieberman J: Micromanipulating cancer: microRNA-based therapeutics?. RNA Biol. 2009, 6: 335-340. 10.4161/rna.6.3.9013.CrossRefPubMed Petrocca F, Lieberman J: Micromanipulating cancer: microRNA-based therapeutics?. RNA Biol. 2009, 6: 335-340. 10.4161/rna.6.3.9013.CrossRefPubMed
26.
go back to reference Wang V, Wu W: MicroRNA-based therapeutics for cancer. BioDrugs. 2009, 23: 15-23. 10.2165/00063030-200923010-00002.CrossRefPubMed Wang V, Wu W: MicroRNA-based therapeutics for cancer. BioDrugs. 2009, 23: 15-23. 10.2165/00063030-200923010-00002.CrossRefPubMed
27.
go back to reference Yousef GM: microRNAs: a new frontier in kallikrein research. Biol Chem. 2008, 389: 689-694. 10.1515/BC.2008.068.CrossRefPubMed Yousef GM: microRNAs: a new frontier in kallikrein research. Biol Chem. 2008, 389: 689-694. 10.1515/BC.2008.068.CrossRefPubMed
Metadata
Title
MicroRNAs: exploring a new dimension in the pathogenesis of kidney cancer
Authors
Nicole MA White
George M Yousef
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2010
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/1741-7015-8-65

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