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28.11.2018 | Original Article

Mitochondrial PIWI-interacting RNAs are novel biomarkers for clear cell renal cell carcinoma

verfasst von: Chenming Zhao, Yuri Tolkach, Doris Schmidt, Marieta Toma, Michael H. Muders, Glen Kristiansen, Stefan C. Müller, Jörg Ellinger

Erschienen in: World Journal of Urology | Ausgabe 8/2019

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Abstract

Purpose

PIWI-interacting RNAs (piRNAs) have been suggested to serve as biomarkers in cancer. In this study, we validated the expression profile of two piRNAs derived from mitochondria, piR-34536 and piR-51810, in tissue and serum of a cohort of clear cell renal cell carcinoma (ccRCC) patients.

Methods

Tissue and serum samples of patients with ccRCC were collected prospectively in our biobank. Total RNA was isolated from 118 ccRCC tissues, 75 normal renal tissues as well as 30 serum samples from patients with ccRCC, and 15 serum samples from patients with non-malignant diseases. The expression of piRNAs was determined using quantitative real-time PCR.

Results

Both piR-34536 and piR-51810 were downregulated in ccRCC compared to non-malignant renal tissue. Decreased tissue piRNA levels were significant and independent predictors of shortened progression-free, cancer-specific and overall survival of ccRCC patients. The piRNA levels in serum did not differ in ccRCC patients and control subjects.

Conclusions

The expression of piR-34536 and piR-51810 in ccRCC tissues may be used as prognostic biomarkers in ccRCC.

Ljungberg B, Campbell SC, Choi HY, Jacqmin D, Lee JE, Weikert S, Kiemeney LA (2011) The epidemiology of renal cell carcinoma. Eur Urol 60(4):615–621. https://doi.org/10.1016/j.eururo.2011.06.049 CrossRefPubMed

Capitanio U, Cloutier V, Zini L, Isbarn H, Jeldres C, Shariat SF, Perrotte P, Antebi E, Patard JJ, Montorsi F, Karakiewicz PI (2009) A critical assessment of the prognostic value of clear cell, papillary and chromophobe histological subtypes in renal cell carcinoma: a population-based study. BJU Int 103(11):1496–1500. https://doi.org/10.1111/j.1464-410X.2008.08259.x CrossRef

Johnson DC, Vukina J, Smith AB, Meyer AM, Wheeler SB, Kuo TM, Tan HJ, Woods ME, Raynor MC, Wallen EM, Pruthi RS, Nielsen ME (2015) Preoperatively misclassified, surgically removed benign renal masses: a systematic review of surgical series and United States population level burden estimate. J Urol 193(1):30–35. https://doi.org/10.1016/j.juro.2014.07.102 CrossRefPubMed

Dabestani S, Marconi L, Kuusk T, Bex A (2018) Follow-up after curative treatment of localised renal cell carcinoma. World J Urol. https://doi.org/10.1007/s00345-018-2338-z CrossRefPubMed

Choueiri TK, Motzer RJ (2017) Systemic therapy for metastatic renal-cell carcinoma. N Engl J Med 376(4):354–366. https://doi.org/10.1056/NEJMra1601333 CrossRefPubMed

Klatte T, Rossi SH, Stewart GD (2018) Prognostic factors and prognostic models for renal cell carcinoma: a literature review. World J Urol. https://doi.org/10.1007/s00345-018-2309-4 CrossRefPubMedPubMedCentral

Sullenger BA, Nair S (2016) From the RNA world to the clinic. Science 352(6292):1417–1420. https://doi.org/10.1126/science.aad8709 CrossRefPubMedPubMedCentral

Ng KW, Anderson C, Marshall EA, Minatel BC, Enfield KS, Saprunoff HL, Lam WL, Martinez VD (2016) Piwi-interacting RNAs in cancer: emerging functions and clinical utility. Mol Cancer 15:5. https://doi.org/10.1186/s12943-016-0491-9 CrossRefPubMedPubMedCentral

Kwon C, Tak H, Rho M, Chang HR, Kim YH, Kim KT, Balch C, Lee EK, Nam S (2014) Detection of PIWI and piRNAs in the mitochondria of mammalian cancer cells. Biochem Biophys Res Commun 446(1):218–223. https://doi.org/10.1016/j.bbrc.2014.02.112 CrossRefPubMed

10.

Chung IF, Chang SJ, Chen CY, Liu SH, Li CY, Chan CH, Shih CC, Cheng WC (2017) YM500v3: a database for small RNA sequencing in human cancer research. Nucleic Acids Res 45(D1):D925–D931. https://doi.org/10.1093/nar/gkw1084 CrossRefPubMed

11.

Blondeau JJ, Deng M, Syring I, Schrodter S, Schmidt D, Perner S, Muller SC, Ellinger J (2015) Identification of novel long non-coding RNAs in clear cell renal cell carcinoma. Clin epigenet 7:10. https://doi.org/10.1186/s13148-015-0047-7 CrossRef

12.

Zhao C, Tolkach Y, Schmidt D, Kristiansen G, Muller SC, Ellinger J (2018) 5′-tRNA halves are dysregulated in clear cell renal cell carcinoma. J Urol 199(2):378–383. https://doi.org/10.1016/j.juro.2017.07.082 CrossRefPubMed

13.

Suzuki R, Honda S, Kirino Y (2012) PIWI expression and function in cancer. Front Genet 3:204. https://doi.org/10.3389/fgene.2012.00204 CrossRefPubMedPubMedCentral

14.

Watanabe T, Lin H (2014) Posttranscriptional regulation of gene expression by Piwi proteins and piRNAs. Mol Cell 56(1):18–27. https://doi.org/10.1016/j.molcel.2014.09.012 CrossRefPubMedPubMedCentral

15.

Fu A, Jacobs DI, Hoffman AE, Zheng T, Zhu Y (2015) PIWI-interacting RNA 021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome. Carcinogenesis 36(10):1094–1102. https://doi.org/10.1093/carcin/bgv105 CrossRefPubMedPubMedCentral

16.

Yin H, Lin H (2007) An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster. Nature 450(7167):304–308. https://doi.org/10.1038/nature06263 CrossRefPubMed

17.

Yang OC, Maxwell PH, Pollard PJ (2013) Renal cell carcinoma: translational aspects of metabolism and therapeutic consequences. Kidney Int 84(4):667–681. https://doi.org/10.1038/ki.2013.245 CrossRefPubMed

18.

Martinez VD, Vucic EA, Thu KL, Hubaux R, Enfield KS, Pikor LA, Becker-Santos DD, Brown CJ, Lam S, Lam WL (2015) Unique somatic and malignant expression patterns implicate PIWI-interacting RNAs in cancer-type specific biology. Sci Rep 5:10423. https://doi.org/10.1038/srep10423 CrossRefPubMedPubMedCentral

19.

Li Y, Wu X, Gao H, Jin JM, Li AX, Kim YS, Pal SK, Nelson RA, Lau CM, Guo C, Mu B, Wang J, Wang F, Wang J, Zhao Y, Chen W, Rossi JJ, Weiss LM, Wu H (2015) Piwi-interacting RNAs (piRNAs) are dysregulated in renal cell carcinoma and associated with tumor metastasis and cancer-specific survival. Mol Med 21:381–388. https://doi.org/10.2119/molmed.2014.00203 CrossRefPubMedPubMedCentral

20.

Busch J, Ralla B, Jung M, Wotschofsky Z, Trujillo-Arribas E, Schwabe P, Kilic E, Fendler A, Jung K (2015) Piwi-interacting RNAs as novel prognostic markers in clear cell renal cell carcinomas. J Exp Clin Cancer Res 34:61. https://doi.org/10.1186/s13046-015-0180-3 CrossRefPubMedPubMedCentral

21.

Iliev R, Fedorko M, Machackova T, Mlcochova H, Svoboda M, Pacik D, Dolezel J, Stanik M, Slaby O (2016) Expression levels of PIWI-interacting RNA, piR-823, are deregulated in tumor tissue, blood serum and urine of patients with renal cell carcinoma. Anticancer Res 36(12):6419–6423. https://doi.org/10.21873/anticanres.11239 CrossRefPubMed

22.

Dietrich D, Meller S, Uhl B, Ralla B, Stephan C, Jung K, Ellinger J, Kristiansen G (2014) Nucleic acid-based tissue biomarkers of urologic malignancies. Crit Rev Clin Lab Sci 51(4):173–199. https://doi.org/10.3109/10408363.2014.906130 CrossRefPubMed

23.

Turajlic S, Xu H, Litchfield K, Rowan A, Horswell S, Chambers T, O’Brien T, Lopez JI, Watkins TBK, Nicol D, Stares M, Challacombe B, Hazell S, Chandra A, Mitchell TJ, Au L, Eichler-Jonsson C, Jabbar F, Soultati A, Chowdhury S, Rudman S, Lynch J, Fernando A, Stamp G, Nye E, Stewart A, Xing W, Smith JC, Escudero M, Huffman A, Matthews N, Elgar G, Phillimore B, Costa M, Begum S, Ward S, Salm M, Boeing S, Fisher R, Spain L, Navas C, Gronroos E, Hobor S, Sharma S, Aurangzeb I, Lall S, Polson A, Varia M, Horsfield C, Fotiadis N, Pickering L, Schwarz RF, Silva B, Herrero J, Luscombe NM, Jamal-Hanjani M, Rosenthal R, Birkbak NJ, Wilson GA, Pipek O, Ribli D, Krzystanek M, Csabai I, Szallasi Z, Gore M, McGranahan N, Van Loo P, Campbell P, Larkin J, Swanton C, TRACERx Renal Consortium (2018) Deterministic evolutionary trajectories influence primary tumor growth: TRACERx renal. Cell 173(3):595–610. https://doi.org/10.1016/j.cell.2018.03.043 CrossRefPubMedPubMedCentral

24.

Saeed K, Ojamies P, Pellinen T, Eldfors S, Turkki R, Lundin J, Jarvinen P, Nisen H, Taari K, af Hallstrom TM, Rannikko A, Mirtti T, Kallioniemi O, Ostling P (2018) Clonal heterogeneity influences drug responsiveness in renal cancer assessed by ex vivo drug testing of multiple patient-derived cancer cells. Int J Cancer. https://doi.org/10.1002/ijc.31815 CrossRefPubMed

Titel: Mitochondrial PIWI-interacting RNAs are novel biomarkers for clear cell renal cell carcinoma
verfasst von: Chenming Zhao
Yuri Tolkach
Doris Schmidt
Marieta Toma
Michael H. Muders
Glen Kristiansen
Stefan C. Müller
Jörg Ellinger
Publikationsdatum: 28.11.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: World Journal of Urology / Ausgabe 8/2019
Print ISSN: 0724-4983
Elektronische ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-018-2575-1

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Mitochondrial PIWI-interacting RNAs are novel biomarkers for clear cell renal cell carcinoma

Abstract

Purpose

Methods

Results

Conclusions

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