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Molecular Biology Reports

, Volume 47, Issue 2, pp 1283–1292 | Cite as

miR-143 expression profiles in urinary bladder cancer: correlation with clinical and epidemiological parameters

  • Nouha Setti Boubaker
  • Manuela Spagnuolo
  • Nesrine Trabelsi
  • Rahma Said
  • Aymone Gurtner
  • Giulia Regazzo
  • Haroun Ayed
  • Ahlem Blel
  • Omar Karray
  • Ahmed Saadi
  • Soumaya Rammeh
  • Mohamed Chebil
  • Maria Giulia Rizzo
  • Giulia PiaggioEmail author
  • Slah OuerhaniEmail author
Original Article

Abstract

Hsa-mir-143 and hsa-let-7c have been reported to be deregulated in multiple neoplasms. The main purpose of this study was to investigate the expression of these miRNAs in bladder cancer (BCa) and to analyze the association between their expression profiles and clinical and epidemiological parameters. Ninety BCa specimens were included. Expression patterns of miR-143 and let-7c were assessed by qRT-PCR using Taqman specific probes. Validated and predicted targets of these miRNA’s were identified using CSmiRTar and DAVID tools, respectively. miR-143 was downregulated in tumors compared to controls (mean fold-change (FC) = 0.076). Its expression was significantly higher in MIBC compared to NMIBC (p = 0,001). Its value as a potential biomarker discriminating non invasive tumors from the invasive ones was confirmed by ROC curve (AUC = 0.768; p = 0.0001). Also, this down-regulation positively correlates with frequency of tobacco use (p = 0,04) and chronic alcohol consumption (p = 0,04). Let-7c was overexpressed in BCa samples (mean (FC = 9.92) compared to non tumoral ones but was not associated to clinical and epidemiological parameters. A comprehensive overview of miR-143 targets and pathways implicated in BCa initiation, diagnosis or prognosis using bioinformatical analysis, was conducted. While both deregulated miRNAs may contribute to urothelial tumorigenesis, the deregulation of miR-143 was significantly correlated to epidemiological and clinical parameters.

Keywords

Urinary bladder neoplasms miRNA pathways biomarkers prognosis 

Notes

Acknowledgements

I would like to thank the medical and paramedical team of the Urology, pathology anatomy and cytology departments, Charles Nicolle Hospital, Tunis, Tunisia. Also all the team of UOSD SAFU, Oncogenomic and Epigenetic Unit and all the people who welcomed me, helped and supported me in Regina Elena National Cancer Institute, Rome, Italy.

Author Contributions

Conceptualization, GP and SO; data curation, NSB, MS, NT and RS; formal analysis, NT and SO; investigation, NSB; methodology, NSB; project administration, HA, GP and SO; resources, HA, AB, OK, SRR, MC, MGR, GP and SO; supervision, SO; validation, MS, AG and GR; visualization, NSB; writing—original draft, NSB; writing—review and editing, RS, HA, OK, GP and SO.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflicts of interest

The authors declare no conflict of interest.

Supplementary material

11033_2019_5228_MOESM1_ESM.docx (322 kb)
Supplementary material 1 (DOCX 321.5 kb)
11033_2019_5228_MOESM2_ESM.docx (54 kb)
Supplementary material 2 (DOCX 54.2 kb)

References

  1. 1.
    Cherif M, Chakroun M, Bouzouita A, Dimassi H, Ayed H, Derouiche A, Ben Slama MR, Chebil M (2016) Caractéristiques épidémiologiques du cancer de la vessie chez la femme en Tunisie. Afr J Urol 22(2):71–75.  https://doi.org/10.1016/j.afju.2015.06.005 CrossRefGoogle Scholar
  2. 2.
    Babjuk M, Bohle A, Burger M, Capoun O, Cohen D, Comperat EM, Hernandez V, Kaasinen E, Palou J, Roupret M, van Rhijn BW, Shariat SF, Soukup V, Sylvester RJ, Zigeuner R (2017) EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol 71(3):447–461.  https://doi.org/10.1016/j.eururo.2016.05.041 CrossRefPubMedGoogle Scholar
  3. 3.
    Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, Kassouf W, Kiemeney LA, La Vecchia C, Shariat S, Lotan Y (2013) Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 63(2):234–241.  https://doi.org/10.1016/j.eururo.2012.07.033 CrossRefPubMedGoogle Scholar
  4. 4.
    Freedman ND, Silverman DT, Hollenbeck AR, Schatzkin A, Abnet CC (2011) Association between smoking and risk of bladder cancer among men and women. Jama 306(7):737–745.  https://doi.org/10.1001/jama.2011.1142 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Botteri E, Ferrari P, Roswall N, Tjonneland A, Hjartaker A, Huerta JM, Fortner RT, Trichopoulou A, Karakatsani A, La Vecchia C (2017) Alcohol consumption and risk of urothelial cell bladder cancer in the European prospective investigation into cancer and nutrition cohort. Int J Cancer 141(10):1963–1970CrossRefGoogle Scholar
  6. 6.
    Rushton L, Hutchings SJ, Fortunato L, Young C, Evans GS, Brown T, Bevan R, Slack R, Holmes P, Bagga S, Cherrie JW, Van Tongeren M (2012) Occupational cancer burden in Great Britain. Br J Cancer 107(Suppl 1):S3–S7.  https://doi.org/10.1038/bjc.2012.112 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    van Kessel KEM, van der Keur KA, Dyrskjot L, Algaba F, Welvaart NYC, Beukers W, Segersten U, Keck B, Maurer T, Simic T, Horstmann M, Grimm MO, Hermann GG, Mogensen K, Hartmann A, Harving N, Petersen AC, Jensen JB, Junker K, Boormans JL, Real FX, Malats N, Malmstrom PU, Orntoft TF, Zwarthoff EC (2018) Molecular markers increase precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups. Clin Cancer Res 24(7):1586–1593.  https://doi.org/10.1158/1078-0432.ccr-17-2719 CrossRefPubMedGoogle Scholar
  8. 8.
    Harb-de la Rosa A, Acker M, Kumar RA, Manoharan M (2015) Epigenetics application in the diagnosis and treatment of bladder cancer. Can J Urol 22(5):7947–7951PubMedGoogle Scholar
  9. 9.
    Catto JW, Alcaraz A, Bjartell AS, De Vere White R, Evans CP, Fussel S, Hamdy FC, Kallioniemi O, Mengual L, Schlomm T, Visakorpi T (2011) MicroRNA in prostate, bladder, and kidney cancer: a systematic review. Eur Urol 59(5):671–681.  https://doi.org/10.1016/j.eururo.2011.01.044 CrossRefPubMedGoogle Scholar
  10. 10.
    Ingelmo-Torres M, Lozano JJ, Izquierdo L, Carrion A, Costa M, Gomez L, Ribal MJ, Alcaraz A, Mengual L (2017) Urinary cell microRNA-based prognostic classifier for non-muscle invasive bladder cancer. Oncotarget 8(11):18238–18247.  https://doi.org/10.18632/oncotarget.15315 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Matsushita R, Seki N, Chiyomaru T, Inoguchi S, Ishihara T, Goto Y, Nishikawa R, Mataki H, Tatarano S, Itesako T, Nakagawa M, Enokida H (2015) Tumour-suppressive microRNA-144-5p directly targets CCNE1/2 as potential prognostic markers in bladder cancer. Br J Cancer 113(2):282–289.  https://doi.org/10.1038/bjc.2015.195 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Huang Y, Li Y, Wang FF, Lv W, Xie X, Cheng X (2016) Over-expressed miR-224 promotes the progression of cervical cancer via targeting RASSF8. PLoS ONE 11(9):e0162378.  https://doi.org/10.1371/journal.pone.0162378 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Chen YH, Wang SQ, Wu XL, Shen M, Chen ZG, Chen XG, Liu YX, Zhu XL, Guo F, Duan XZ, Han XC, Tao ZH (2013) Characterization of microRNAs expression profiling in one group of Chinese urothelial cell carcinoma identified by Solexa sequencing. Urol Oncol 31(2):219–227.  https://doi.org/10.1016/j.urolonc.2010.11.007 CrossRefPubMedGoogle Scholar
  14. 14.
    Wang H, Li Q, Niu X, Wang G, Zheng S, Fu G, Wang Z (2017) miR-143 inhibits bladder cancer cell proliferation and enhances their sensitivity to gemcitabine by repressing IGF-1R signaling. Oncol Lett 13(1):435–440.  https://doi.org/10.3892/ol.2016.5388 CrossRefPubMedGoogle Scholar
  15. 15.
    Balzeau J, Menezes MR, Cao S, Hagan JP (2017) The LIN28/let-7 pathway in cancer. Front Genet 8:31.  https://doi.org/10.3389/fgene.2017.00031 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ (2005) RAS is regulated by the let-7 microRNA family. Cell 120(5):635–647.  https://doi.org/10.1016/j.cell.2005.01.014 CrossRefPubMedGoogle Scholar
  17. 17.
    Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T (2007) Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 39(5):673–677.  https://doi.org/10.1038/ng2003 CrossRefPubMedGoogle Scholar
  18. 18.
    Mayr C, Hemann MT, Bartel DP (2007) Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science 315(5818):1576–1579.  https://doi.org/10.1126/science.1137999 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Vinall RL, Tepper CG, Ripoll AA, Gandour-Edwards RF, Durbin-Johnson BP, Yap SA, Ghosh PM, deVere White RW (2016) Decreased expression of let-7c is associated with non-response of muscle-invasive bladder cancer patients to neoadjuvant chemotherapy. Genes cancer 7(3–4):86–97.  https://doi.org/10.18632/genesandcancer.103 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Gilles ME, Slack FJ (2018) Let-7 microRNA as a potential therapeutic target with implications for immunotherapy. Expert Opin Ther Targets 22(11):929–939.  https://doi.org/10.1080/14728222.2018.1535594 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Avgeris M, Mavridis K, Tokas T, Stravodimos K, Fragoulis EG, Scorilas A (2015) Uncovering the clinical utility of miR-143, miR-145 and miR-224 for predicting the survival of bladder cancer patients following treatment. Carcinogenesis 36(5):528–537.  https://doi.org/10.1093/carcin/bgv024 CrossRefPubMedGoogle Scholar
  22. 22.
    Sachdeva M, Zhu S, Wu F, Wu H, Walia V, Kumar S, Elble R, Watabe K, Mo YY (2009) p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci USA 106(9):3207–3212.  https://doi.org/10.1073/pnas.0808042106 CrossRefPubMedGoogle Scholar
  23. 23.
    Lin T, Dong W, Huang J, Pan Q, Fan X, Zhang C, Huang L (2009) MicroRNA-143 as a tumor suppressor for bladder cancer. J Urol 181(3):1372–1380.  https://doi.org/10.1016/j.juro.2008.10.149 CrossRefPubMedGoogle Scholar
  24. 24.
    Noguchi S, Yasui Y, Iwasaki J, Kumazaki M, Yamada N, Naito S, Akao Y (2013) Replacement treatment with microRNA-143 and – 145 induces synergistic inhibition of the growth of human bladder cancer cells by regulating PI3K/Akt and MAPK signaling pathways. Cancer Lett 328(2):353–361.  https://doi.org/10.1016/j.canlet.2012.10.017 CrossRefPubMedGoogle Scholar
  25. 25.
    Esau C, Kang X, Peralta E, Hanson E, Marcusson EG, Ravichandran LV, Sun Y, Koo S, Perera RJ, Jain R, Dean NM, Freier SM, Bennett CF, Lollo B, Griffey R (2004) MicroRNA-143 regulates adipocyte differentiation. J Biol Chem 279(50):52361–52365.  https://doi.org/10.1074/jbc.C400438200 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Liu X, Zhao W, Wang X, Zhu Y, Zhou Z, Shi B (2019) Expression of mir-143 in serum of bladder cancer patients and its correlation with clinical features and prognosis. J BUON 24(2):791–796PubMedGoogle Scholar
  27. 27.
    Puerta-Gil P, Garcia-Baquero R, Jia AY, Ocana S, Alvarez-Mugica M, Alvarez-Ossorio JL, Cordon-Cardo C, Cava F, Sanchez-Carbayo M (2012) miR-143, miR-222, and miR-452 are useful as tumor stratification and noninvasive diagnostic biomarkers for bladder cancer. Am J Pathol 180(5):1808–1815.  https://doi.org/10.1016/j.ajpath.2012.01.034 CrossRefPubMedGoogle Scholar
  28. 28.
    Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI, Alder H, Volinia S, Rassenti L, Liu X, Liu CG, Kipps TJ, Negrini M, Croce CM (2008) MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci USA 105(13):5166–5171.  https://doi.org/10.1073/pnas.0800121105 CrossRefPubMedGoogle Scholar
  29. 29.
    Zhang B, Pan X, Cobb GP, Anderson TA (2007) microRNAs as oncogenes and tumor suppressors. Dev Biol 302(1):1–12.  https://doi.org/10.1016/j.ydbio.2006.08.028 CrossRefPubMedGoogle Scholar
  30. 30.
    DeVere White RW, Vinall RL, Tepper CG, Shi XB (2009) MicroRNAs and their potential for translation in prostate cancer. Urol Oncol 27(3):307–311.  https://doi.org/10.1016/j.urolonc.2009.01.004 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 103(7):2257–2261.  https://doi.org/10.1073/pnas.0510565103 CrossRefPubMedGoogle Scholar
  32. 32.
    Nair VS, Maeda LS, Ioannidis JPA (2012) Clinical outcome prediction by MicroRNAs in human cancer: a systematic review. JNCI J Natl Cancer Inst 104(7):528–540.  https://doi.org/10.1093/jnci/djs027 CrossRefPubMedGoogle Scholar
  33. 33.
    Bertz S, Eckstein M, Stoehr R, Weyerer V, Hartmann A (2017) Urothelial bladder cancer: an update on molecular pathology with clinical implications. Eur Urol Suppl 16(12):272–294.  https://doi.org/10.1016/j.eursup.2017.10.003 CrossRefGoogle Scholar
  34. 34.
    Banwait JK, Bastola DR (2015) Contribution of bioinformatics prediction in microRNA-based cancer therapeutics. Adv Drug Deliv Rev 81:94–103.  https://doi.org/10.1016/j.addr.2014.10.030 CrossRefPubMedGoogle Scholar
  35. 35.
    Dip N, Reis ST, Viana NI, Morais DR, Moura CM, Katz B, Abe DK, Iscaife A, Silva IA, Srougi M (2014) MiRNA in bladder carcinogenesis: a review. World J Clin Urol 3(3):238–248CrossRefGoogle Scholar
  36. 36.
    Song T, Xia W, Shao N, Zhang X, Wang C, Wu Y, Dong J, Cai W, Li H (2010) Differential miRNA expression profiles in bladder urothelial carcinomas. Asian Pac J Cancer Prev APJCP 11(4):905–911PubMedGoogle Scholar
  37. 37.
    Zhang Q, Feng Y, Liu P, Yang J (2017) MiR-143 inhibits cell proliferation and invasion by targeting DNMT3A in gastric cancer. Tumour Biol 39(7):1010428317711312.  https://doi.org/10.1177/1010428317711312 CrossRefPubMedGoogle Scholar
  38. 38.
    Hossian A, Sajib MS, Tullar PE, Mikelis CM, Mattheolabakis G (2018) Multipronged activity of combinatorial miR-143 and miR-506 inhibits Lung Cancer cell cycle progression and angiogenesis in vitro. Sci Rep 8(1):10495.  https://doi.org/10.1038/s41598-018-28872-2 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Piatopoulou D, Avgeris M, Drakaki I, Marmarinos A, Xagorari M, Baka M, Pourtsidis A, Kossiva L, Gourgiotis D, Scorilas A (2018) Clinical utility of miR-143/miR-182 levels in prognosis and risk stratification specificity of BFM-treated childhood acute lymphoblastic leukemia. Ann Hematol 97(7):1169–1182.  https://doi.org/10.1007/s00277-018-3292-y CrossRefPubMedGoogle Scholar
  40. 40.
    Reshmi G, Pillai MR (2008) Beyond HPV: oncomirs as new players in cervical cancer. FEBS Lett 582(30):4113–4116.  https://doi.org/10.1016/j.febslet.2008.11.011 CrossRefPubMedGoogle Scholar
  41. 41.
    Pignot G, Cizeron-Clairac G, Vacher S, Susini A, Tozlu S, Vieillefond A, Zerbib M, Lidereau R, Debre B, Amsellem-Ouazana D, Bieche I (2013) microRNA expression profile in a large series of bladder tumors: identification of a 3-miRNA signature associated with aggressiveness of muscle-invasive bladder cancer. Int J Cancer 132(11):2479–2491.  https://doi.org/10.1002/ijc.27949 CrossRefPubMedGoogle Scholar
  42. 42.
    Qian X, Yu J, Yin Y, He J, Wang L, Li Q, Zhang LQ, Li CY, Shi ZM, Xu Q, Li W, Lai LH, Liu LZ, Jiang BH (2013) MicroRNA-143 inhibits tumor growth and angiogenesis and sensitizes chemosensitivity to oxaliplatin in colorectal cancers. Cell Cycle (Georgetown Tex) 12(9):1385–1394.  https://doi.org/10.4161/cc.24477 CrossRefGoogle Scholar
  43. 43.
    Eissa S, Ali HS, Al Tonsi AH, Zaglol A, El Ahmady O (2005) HER2/neu expression in bladder cancer: relationship to cell cycle kinetics. Clin Biochem 38(2):142–148.  https://doi.org/10.1016/j.clinbiochem.2004.09.004 CrossRefPubMedGoogle Scholar
  44. 44.
    Kompier LC, Lurkin I, van der Aa MN, van Rhijn BW, van der Kwast TH, Zwarthoff EC (2010) FGFR3, HRAS, KRAS, NRAS and PIK3CA mutations in bladder cancer and their potential as biomarkers for surveillance and therapy. PLoS ONE 5(11):e13821.  https://doi.org/10.1371/journal.pone.0013821 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Nagata M, Muto S, Horie S (2016) Molecular biomarkers in bladder cancer: novel potential indicators of prognosis and treatment outcomes. Dis Markers 2016:8205836–8205836.  https://doi.org/10.1155/2016/8205836 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Kumar B, Sinclair J, Khandrika L, Koul S, Wilson S, Koul HK (2009) Differential effects of MAPKs signaling on the growth of invasive bladder cancer cells. Int J Oncol 34(6):1557–1564.  https://doi.org/10.3892/ijo_00000285 CrossRefPubMedGoogle Scholar
  47. 47.
    Sathe A, Nawroth R (2018) Targeting the PI3K/AKT/mTOR pathway in bladder cancer. Methods Mol Biol (Clifton NJ) 1655:335–350.  https://doi.org/10.1007/978-1-4939-7234-0_23 CrossRefGoogle Scholar
  48. 48.
    Farhan M, Wang H, Gaur U, Little PJ, Xu J, Zheng W (2017) FOXO signaling pathways as therapeutic targets in cancer. Int J Biol Sci 13(7):815–827.  https://doi.org/10.7150/ijbs.20052 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Askeland EJ, Newton MR, O’Donnell MA, Luo Y (2012) Bladder cancer immunotherapy: BCG and beyond. Adv Urol 2012:181987–181987.  https://doi.org/10.1155/2012/181987 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Batliner J, Buehrer E, Fey MF, Tschan MP (2012) Inhibition of the miR-143/145 cluster attenuated neutrophil differentiation of APL cells. Leukemia Res 36(2):237–240.  https://doi.org/10.1016/j.leukres.2011.10.006 CrossRefGoogle Scholar
  51. 51.
    Bywater MJ, Pearson RB, McArthur GA, Hannan RD (2013) Dysregulation of the basal RNA polymerase transcription apparatus in cancer. Nat Rev Cancer 13:299.  https://doi.org/10.1038/nrc3496 CrossRefPubMedGoogle Scholar
  52. 52.
    Ouerhani S, Rouissi K, Kourda N, Marrakchi R, Bougatef K, Riadh Ben Slama M, Sfaxi M, Chebil M, Ben Jilani S, Benammar Elgaaied A (2009) Combined analysis of smoking, TP53, and FGFR3 mutations in Tunisian patients with invasive and superficial high-grade bladder tumors. Cancer Investig 27(10):998–1007.  https://doi.org/10.3109/07357900902849707 CrossRefGoogle Scholar
  53. 53.
    Han Y, Chen J, Zhao X, Liang C, Wang Y, Sun L, Jiang Z, Zhang Z, Yang R, Chen J, Li Z, Tang A, Li X, Ye J, Guan Z, Gui Y, Cai Z (2011) MicroRNA expression signatures of bladder cancer revealed by deep sequencing. PLoS ONE 6(3):e18286.  https://doi.org/10.1371/journal.pone.0018286 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Yoshino H, Chiyomaru T, Enokida H, Kawakami K, Tatarano S, Nishiyama K, Nohata N, Seki N, Nakagawa M (2011) The tumour-suppressive function of miR-1 and miR-133a targeting TAGLN2 in bladder cancer. Br J Cancer 104(5):808–818.  https://doi.org/10.1038/bjc.2011.23 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Catto JW, Miah S, Owen HC, Bryant H, Myers K, Dudziec E, Larre S, Milo M, Rehman I, Rosario DJ, Di Martino E, Knowles MA, Meuth M, Harris AL, Hamdy FC (2009) Distinct microRNA alterations characterize high- and low-grade bladder cancer. Cancer Res 69(21):8472–8481.  https://doi.org/10.1158/0008-5472.can-09-0744 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Nouha Setti Boubaker
    • 1
    • 3
  • Manuela Spagnuolo
    • 2
  • Nesrine Trabelsi
    • 1
  • Rahma Said
    • 1
  • Aymone Gurtner
    • 3
  • Giulia Regazzo
    • 2
  • Haroun Ayed
    • 1
    • 4
  • Ahlem Blel
    • 5
  • Omar Karray
    • 4
  • Ahmed Saadi
    • 1
    • 4
  • Soumaya Rammeh
    • 5
  • Mohamed Chebil
    • 4
  • Maria Giulia Rizzo
    • 2
  • Giulia Piaggio
    • 3
    Email author
  • Slah Ouerhani
    • 1
    Email author
  1. 1.Laboratory of Proteins Engineering and Bioactive Molecules (LIP-MB), National Institute of Applied Sciences and Technology of Tunis (INSAT)The University of Tunis CarthageTunisTunisia
  2. 2.Oncogenomic and Epigenetic Unit, Department of Research, Diagnosis and Innovative TechnologiesIRCCS-Regina Elena National Cancer InstituteRomeItaly
  3. 3.Department of Research, Diagnosis and Innovative Technologies, IRCCS-Regina Elena National Cancer InstituteUOSD SAFURomeItaly
  4. 4.Urology DepartmentCharles Nicolle HospitalTunisTunisia
  5. 5.Pathology DepartmentCharles Nicolle HospitalTunisTunisia

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