Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Urology
Published in: BMC Urology 1/2017

Open Access 01-12-2017 | Research article

Expression of micro-RNAs and genes related to angiogenesis in ccRCC and associations with tumor characteristics

Authors: Rita de Cássia Oliveira, Renato Fidelis Ivanovic, Katia Ramos Moreira Leite, Nayara Izabel Viana, Ruan César Aparecido Pimenta, José Pontes Junior, Vanessa Ribeiro Guimarães, Denis Reis Morais, Daniel Kanda Abe, Adriano João Nesrallah, Miguel Srougi, William Nahas, Sabrina Thalita Reis

Published in: BMC Urology | Issue 1/2017

Login to get access

Abstract

Background

Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer in adults. Our aim is to evaluate genes and miRNAs expression profiles involved with angiogenesis and tumor characteristics in ccRCC.

Methods

The expression levels of miRNAs miR-99a, 99b, 100; 199a; 106a; 106b; 29a; 29b; 29c; 126; 200a, 200b and their respective target genes: mTOR, HIF1-α, VHL, PDGF, VEGF, VEGFR1 and VEGFR2 were analyzed using qRT-PCR in tumor tissue samples from 56 patients with ccRCC. Five samples of benign renal tissue were utilized as control. The expression levels of miRNAs and genes were related to tumor size, Fuhrman nuclear grade and microvascular invasion.

Results

miR99a was overexpressed in most samples and its target gene mTOR was underexpressed, this also occurs for miRNAs 106a, 106b, and their target gene VHL. An increase in miR-200b was correlated with high-risk tumors (p = 0.01) while miR-126 overexpression was associated with Fuhrman’s low grade (p = 0.03).

Conclusions

Our results show that in ccRCC there are changes in miRNAs expression affecting gene expression that could be important in determining the aggressiveness of this lethal neoplasia.
Literature
1.
Bukowski RM. Prognostic factors for survival in metastatic renal cell carcinoma: update 2008. Cancer. 2009;115(10 Suppl):2273–81.CrossRefPubMed
2.
Schaefer A, Stephan C, Busch J, Yousef GM, Jung K. Diagnostic, prognostic and therapeutic implications of microRNAs in urologic tumors. Nature reviews Urology. 2010;7(5):286–97.CrossRefPubMed
3.
4.
5.
Bridge G, Monteiro R, Henderson S, Emuss V, Lagos D, Georgopoulou D, Patient R, Boshoff C. The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis. Blood. 2012;120(25):5063–72.CrossRefPubMed
6.
Catto JW, Alcaraz A, Bjartell AS, De Vere White R, Evans CP, Fussel S, Hamdy FC, Kallioniemi O, Mengual L, Schlomm T, et al. MicroRNA in prostate, bladder, and kidney cancer: a systematic review. Eur Urol. 2011;59(5):671–81.CrossRefPubMed
7.
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(1):4–13.CrossRefPubMed
8.
Ru Y, Dancik GM, Theodorescu D. Biomarkers for prognosis and treatment selection in advanced bladder cancer patients. Curr Opin Urol. 2011;21(5):420–7.CrossRefPubMedCentralPubMed
9.
Fendler A, Stephan C, Yousef GM, Jung K. MicroRNAs as regulators of signal transduction in urological tumors. Clin Chem. 2011;57(7):954–68.CrossRefPubMed
10.
Longo R, D'Andrea MR, Sarmiento R, Salerno F, Gasparini G. Integrated therapy of kidney cancer. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2007;6(18 Suppl):vi141–8.
11.
Smaldone MC, Maranchie JK. Clinical implications of hypoxia inducible factor in renal cell carcinoma. Urol Oncol. 2009;27(3):238–45.CrossRefPubMed
12.
13.
van Solingen C, Seghers L, Bijkerk R, Duijs JM, Roeten MK, van Oeveren-Rietdijk AM, Baelde HJ, Monge M, Vos JB, de Boer HC, et al. Antagomir-mediated silencing of endothelial cell specific microRNA-126 impairs ischemia-induced angiogenesis. J Cell Mol Med. 2009;13(8A):1577–85.CrossRefPubMed
14.
Grundmann S, Hans FP, Kinniry S, Heinke J, Helbing T, Bluhm F, Sluijter JP, Hoefer I, Pasterkamp G, Bode C, et al. MicroRNA-100 regulates neovascularization by suppression of mammalian target of rapamycin in endothelial and vascular smooth muscle cells. Circulation. 2011;123(9):999–1009.CrossRefPubMed
15.
Roy S, Sen CK: miRNA in wound inflammation and angiogenesis. Microcirculation (New York, NY : 1994) 2012, 19(3):224–232.
16.
Li Y, Fan L, Liu S, Liu W, Zhang H, Zhou T, Wu D, Yang P, Shen L, Chen J, et al. The promotion of bone regeneration through positive regulation of angiogenic-osteogenic coupling using microRNA-26a. Biomaterials. 2013;34(21):5048–58.CrossRefPubMed
17.
Zaravinos A, Radojicic J, Lambrou GI, Volanis D, Delakas D, Stathopoulos EN, Spandidos DA. Expression of miRNAs involved in angiogenesis, tumor cell proliferation, tumor suppressor inhibition, epithelial-mesenchymal transition and activation of metastasis in bladder cancer. J Urol. 2012;188(2):615–23.CrossRefPubMed
18.
Yuan HX, Zhang JP, Kong WT, Liu YJ, Lin ZM, Wang WP, Guo JM. Elevated microRNA-185 is associated with high vascular endothelial growth factor receptor 2 expression levels and high microvessel density in clear cell renal cell carcinoma. Tumour Biol. 2014;35(12):12757–63.CrossRefPubMed
19.
Dall'Oglio MF, Antunes AA, Sarkis AS, Crippa A, Leite KR, Lucon AM, Srougi M. Microvascular tumour invasion in renal cell carcinoma: the most important prognostic factor. BJU Int. 2007;100(3):552–5.CrossRefPubMed
20.
Miyamoto H, Miller JS, Fajardo DA, Lee TK, Netto GJ, Epstein JI. Non-invasive papillary urothelial neoplasms: the 2004 WHO/ISUP classification system. Pathol Int. 2010;60(1):1–8.CrossRefPubMed
21.
Montironi R, Santinelli A, Pomante R, Mazzucchelli R, Colanzi P, Filho AL, Scarpelli M. Morphometric index of adult renal cell carcinoma. Comparison with the Fuhrman grading system. Virchows Archiv : an international journal of pathology. 2000;437(1):82–9.CrossRef
22.
23.
Ebbinghaus SW, Gordon MS. Renal cell carcinoma: rationale and development of therapeutic inhibitors of angiogenesis. Hematol Oncol Clin North Am. 2004;18(5):1143–59. ix-xCrossRefPubMed
24.
Choueiri TK, Bukowski RM, Rini BI. The current role of angiogenesis inhibitors in the treatment of renal cell carcinoma. Semin Oncol. 2006;33(5):596–606.CrossRefPubMed
25.
Ljungberg BJ, Jacobsen J, Rudolfsson SH, Lindh G, Grankvist K, Rasmuson T. Different vascular endothelial growth factor (VEGF), VEGF-receptor 1 and −2 mRNA expression profiles between clear cell and papillary renal cell carcinoma. BJU Int. 2006;98(3):661–7.CrossRefPubMed
26.
Posadas EM, Limvorasak S, Sharma S, Figlin RA. Targeting angiogenesis in renal cell carcinoma. Expert Opin Pharmacother. 2013;14(16):2221–36.CrossRefPubMed
27.
Djordjevic G, Mozetic V, Mozetic DV, Licul V, Ilijas KM, Mustac E, Oguic R, Fuckar Z, Jonjic N. Prognostic significance of vascular endothelial growth factor expression in clear cell renal cell carcinoma. Pathol Res Pract. 2007;203(2):99–106.CrossRefPubMed
28.
Berghoff AS, Ilhan-Mutlu A, Dinhof C, Magerle M, Hackl M, Widhalm G, Hainfellner JA, Dieckmann K, Pichler J, Hutterer M, et al. Differential role of angiogenesis and tumour cell proliferation in brain metastases according to primary tumour type: analysis of 639 cases. Neuropathol Appl Neurobiol. 2015;41(2):e41–55.CrossRefPubMed
29.
Wang W, Qi L, Tan M, Zhang Z, Du J, Wei X, Yao X. Effect of platelet-derived growth factor-B on renal cell carcinoma growth and progression. Urologic oncology. 2015;33(4):168.e117–27.CrossRef
30.
Haddad AQ, Kapur P, Singla N, Raman JD, Then MT, Nuhn P, Buchner A, Bastian P, Seitz C, Shariat SF, et al. Validation of mammalian target of rapamycin biomarker panel in patients with clear cell renal cell carcinoma. Cancer. 2015;121(1):43–50.CrossRefPubMed
31.
Bui MH, Zisman A, Pantuck AJ, Han KR, Wieder J, Belldegrun AS. Prognostic factors and molecular markers for renal cell carcinoma. Expert Rev Anticancer Ther. 2001;1(4):565–75.CrossRefPubMed
32.
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. 2010;43(1–2):150–8.CrossRefPubMed
33.
Khella HW, White NM, Faragalla H, Gabril M, Boazak M, Dorian D, Khalil B, Antonios H, Bao TT, Pasic MD, et al. Exploring the role of miRNAs in renal cell carcinoma progression and metastasis through bioinformatic and experimental analyses. Tumour Biol. 2012;33(1):131–40.CrossRefPubMed
34.
35.
Harris TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci U S A. 2008;105(5):1516–21.CrossRefPubMedCentralPubMed
36.
Wong QW, Lung RW, Law PT, Lai PB, Chan KY, To KF, Wong N. MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1. Gastroenterology. 2008;135(1):257–69.CrossRefPubMed
37.
Silva-Santos RM, Costa-Pinheiro P, Luis A, Antunes L, Lobo F, Oliveira J, Henrique R, Jeronimo C. MicroRNA profile: a promising ancillary tool for accurate renal cell tumour diagnosis. Br J Cancer. 2013;109(10):2646–53.CrossRefPubMedCentralPubMed
38.
Katz B, Reis ST, Viana NI, Morais DR, Moura CM, Dip N, Silva IA, Iscaife A, Srougi M, Leite KR. Comprehensive study of gene and microRNA expression related to epithelial-mesenchymal transition in prostate cancer. PLoS One. 2014;9(11):e113700.CrossRefPubMedCentralPubMed
39.
40.
Slaby O, Jancovicova J, Lakomy R, Svoboda M, Poprach A, Fabian P, Kren L, Michalek J, Vyzula R. Expression of miRNA-106b in conventional renal cell carcinoma is a potential marker for prediction of early metastasis after nephrectomy. Journal of experimental & clinical cancer research : CR. 2010;29:90.CrossRefPubMedCentral
41.
Cui L, Zhou H, Zhao H, Zhou Y, Xu R, Xu X, Zheng L, Xue Z, Xia W, Zhang B, et al. MicroRNA-99a induces G1-phase cell cycle arrest and suppresses tumorigenicity in renal cell carcinoma. BMC Cancer. 2012;12:546.CrossRefPubMedCentralPubMed
Metadata
Title
Expression of micro-RNAs and genes related to angiogenesis in ccRCC and associations with tumor characteristics
Authors
Rita de Cássia Oliveira
Renato Fidelis Ivanovic
Katia Ramos Moreira Leite
Nayara Izabel Viana
Ruan César Aparecido Pimenta
José Pontes Junior
Vanessa Ribeiro Guimarães
Denis Reis Morais
Daniel Kanda Abe
Adriano João Nesrallah
Miguel Srougi
William Nahas
Sabrina Thalita Reis
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Urology / Issue 1/2017
Electronic ISSN: 1471-2490
DOI
https://doi.org/10.1186/s12894-017-0306-3

Other articles of this Issue 1/2017

BMC Urology 1/2017 Go to the issue

Case report

A rare diaphragmatic ureteral herniation case report: endoscopic and open reconstructive management

Research article

Anti-tumor effects of a recombinant anti-prostate specific membrane antigen immunotoxin against prostate cancer cells

Research article

Anti-proliferative potential of Glucosamine in renal cancer cells via inducing cell cycle arrest at G0/G1 phase

Research article

Aortic calcification burden predicts deterioration of renal function after radical nephrectomy

Research article

Can Randall’s plug composed of calcium oxalate form via the free particle mechanism?

Research article

The R.I.R.S. scoring system: An innovative scoring system for predicting stone-free rate following retrograde intrarenal surgery