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Article

DKC1 serves as a potential prognostic biomarker for human clear cell renal cell carcinoma and promotes its proliferation, migration and invasion via the NF‑κB pathway

  • Authors:
    • Meng Zhang
    • Yu Pan
    • Ranran Jiang
    • Pingfu Hou
    • Haixia Shan
    • Fang Chen
    • Tao Jiang
    • Jin Bai
    • Junnian Zheng
  • View Affiliations / Copyright

    Affiliations: Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China
  • Pages: 968-978
    |
    Published online on: June 11, 2018
       https://doi.org/10.3892/or.2018.6484
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Abstract

DKC1, an X‑linked gene encoding dyskerin at Xq28, is a crucial component of the telomerase complex and is indispensable for normal telomere function and the post‑­transcriptional modification of precursor rRNA. It has been revealed to exert diverse biological functions and prognostic values in numerous types of cancers. Our present study was aimed at examining DKC1 expression in normal renal tissues and clear cell renal cell carcinoma (ccRCC) samples and the prognostic value of DKC1 in ccRCC. We examined DKC1 protein expression levels in tissue microarrays including 307 cases of ccRCC tissues and in 75 pairs of ccRCC and paracancerous tissues with immunohistochemistry. The percentage of DKC1 expression in ccRCC (61.3%) was markedly higher than that in paracancerous tissues (34.7%) (P=0.001). Positive DKC1 expression tends to significantly be associated with unfavorable clinicopathological characteristics such as tumor diameter >7 cm (P=0.002) and tumor‑node‑metastasis (TNM) stage III or IV (P<0.001). Multivariate COX analysis revealed that positive DKC1 expression was an independent unfavorable factor for prognosis of ccRCC patients [hazard ratio (HR)=1.932, 95% CI, 1.290‑2.893, P=0.001 for 5‑year overall survival; HR=1.778, 95% CI,1.150‑2.748, P=0.010 for disease‑free survival]. In the PROGgeneV2 platform, we also found that ccRCC patients with high DKC1 mRNA expression had a poorer prognosis than patients with low DKC1 expression in The Cancer Genome Atlas (TCGA). Furthermore, we found that knockdown of DKC1 inhibited proliferation, migration and invasion of ccRCC through regulation of the NF‑κB/MMP‑2 signaling pathway in vitro. We also demonstrated that DKC1 regulated ccRCC proliferation and the expression of NF‑κB‑p65 and MMP‑2 in vivo. In summary, the expression of DKC1 was upregulated in ccRCC, which was associated with unfavorable clinicopathological characteristics and DKC1 may act as an independent prognostic indicator of ccRCC patients.
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1 

Volpe A and Patard JJ: Prognostic factors in renal cell carcinoma. World J Urol. 28:319–327. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Rini BI, Campbell SC and Escudier B: Renal cell carcinoma. Lancet. 373:1119–1132. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Lu X, Gu W, Zhang H, Zhu Y, Shi G and Ye D: Oligometastatic state predicts a favorable outcome for renal cell carcinoma patients with bone metastasis under the treatment of sunitinib. Oncotarget. 7:26879–26887. 2016.PubMed/NCBI

4 

Singer EA, Gupta GN and Srinivasan R: Update on targeted therapies for clear cell renal cell carcinoma. Curr Opin Oncol. 23:283–289. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Heiss NS, Knight SW, Vulliamy TJ, Klauck SM, Wiemann S, Mason PJ, Poustka A and Dokal I: X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nat Genet. 19:32–38. 1998. View Article : Google Scholar : PubMed/NCBI

6 

Kirwan M and Dokal I: Dyskeratosis congenita: A genetic disorder of many faces. Clin Genet. 73:103–112. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Sieron P, Hader C, Hatina J, Engers R, Wlazlinski A, Müller M and Schulz WA: DKC1 overexpression associated with prostate cancer progression. Br J Cancer. 101:1410–1416. 2009. View Article : Google Scholar : PubMed/NCBI

8 

O'Brien R, Tran SL, Maritz MF, Liu B, Kong CF, Purgato S, Yang C, Murray J, Russell AJ, Flemming CL, et al: MYC-Driven neuroblastomas are addicted to a telomerase-independent function of dyskerin. Cancer Res. 76:3604–3617. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Liu B, Zhang JL, Huang C and Liu H: Dyskerin overexpression in human hepatocellular carcinoma is associated with advanced clinical stage and poor patient prognosis. PloS one. 7:e431472012. View Article : Google Scholar : PubMed/NCBI

10 

Bellodi C, Krasnykh O, Haynes N, Theodoropoulou M, Peng G, Montanaro L and Ruggero D: Loss of function of the tumor suppressor DKC1 perturbs p27 translation control and contributes to pituitary tumorigenesis. Cancer Res. 70:6026–6035. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Montanaro L, Calienni M, Bertoni S, Rocchi L, Sansone P, Storci G, Santini D, Ceccarelli C, Taffurelli M, Carnicelli D, et al: Novel dyskerin-mediated mechanism of p53 inactivation through defective mRNA translation. Cancer Res. 70:4767–4777. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Mei P, Bai J, Shi M, Liu Q, Li Z, Fan Y and Zheng J: BRMS1 suppresses glioma progression by regulating invasion, migration and adhesion of glioma cells. PloS One. 9:e985442014. View Article : Google Scholar : PubMed/NCBI

13 

Bai J, Yong HM, Chen FF, Song WB, Li C, Liu H and Zheng JN: RUNX3 is a prognostic marker and potential therapeutic target in human breast cancer. J Cancer Res Clin Oncol. 139:1813–1823. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Bai J, Zhou Y, Chen G, Zeng J, Ding J, Tan Y, Zhou J and Li G: Overexpression of Cullin1 is associated with poor prognosis of patients with gastric cancer. Hum Pathol. 42:375–383. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Karin M: Nuclear factor-kappaB in cancer development and progression. Nature. 441:431–436. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Takeshita H, Yoshizaki T, Miller WE, Sato H, Furukawa M, Pagano JS and Raab-Traub N: Matrix metalloproteinase 9 expression is induced by Epstein-Barr virus latent membrane protein 1 C-terminal activation regions 1 and 2. J Virol. 73:5548–5555. 1999.PubMed/NCBI

17 

Cully M, You H, Levine AJ and Mak TW: Beyond PTEN mutations: The PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer. 6:184–192. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Huang S, Robinson JB, Deguzman A, Bucana CD and Fidler IJ: Blockade of nuclear factor-kappaB signaling inhibits angiogenesis and tumorigenicity of human ovarian cancer cells by suppressing expression of vascular endothelial growth factor and interleukin 8. Cancer Res. 60:5334–5339. 2000.PubMed/NCBI

19 

Audenet F, Yates DR, Cancel-Tassin G, Cussenot O and Roupret M: Genetic pathways involved in carcinogenesis of clear cell renal cell carcinoma: Genomics towards personalized medicine. BJU Int. 109:1864–1870. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Mochizuki Y, He J, Kulkarni S, Bessler M and Mason PJ: Mouse dyskerin mutations affect accumulation of telomerase RNA and small nucleolar RNA, telomerase activity, and ribosomal RNA processing. Proc Natl Acad Sci USA. 101:10756–10761. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Filipowicz W and Pogacic V: Biogenesis of small nucleolar ribonucleoproteins. Curr Opin Cell Boil. 14:319–327. 2002. View Article : Google Scholar

22 

Westermann F, Henrich KO, Wei JS, Lutz W, Fischer M, König R, Wiedemeyer R, Ehemann V, Brors B, Ernestus K, et al: High Skp2 expression characterizes high-risk neuroblastomas independent of MYCN status. Clin Cancer Res. 13:4695–4703. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Schaner ME, Ross DT, Ciaravino G, Sorlie T, Troyanskaya O, Diehn M, Wang YC, Duran GE, Sikic TL, Caldeira S, et al: Gene expression patterns in ovarian carcinomas. Mol Boil Cell. 14:4376–4386. 2003. View Article : Google Scholar

24 

Poncet D, Belleville A, t'kint de Roodenbeke C, Roborel de Climens A, Ben Simon E, Merle-Beral H, Callet-Bauchu E, Salles G, Sabatier L, Delic J and Gilson E: Changes in the expression of telomere maintenance genes suggest global telomere dysfunction in B-chronic lymphocytic leukemia. Blood. 111:2388–2391. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Lowe SW: Cancer therapy and p53. Curr Opin Oncol. 7:547–553. 1995. View Article : Google Scholar : PubMed/NCBI

26 

Lowe SW, Bodis S, McClatchey A, Remington L, Ruley HE, Fisher DE, Housman DE and Jacks T: p53 status and the efficacy of cancer therapy in vivo. Science. 266:807–810. 1994. View Article : Google Scholar : PubMed/NCBI

27 

Tomasino RM, Morello V, Tralongo V, Nagar C, Nuara R, Daniele E, Curti M and Orestano F: p53 expression in human renal cell carcinoma: An immunohistochemical study and a literature outline of the cytogenetic characterization. Pathologica. 86:227–233. 1994.PubMed/NCBI

28 

von Stedingk K, Koster J, Piqueras M, Noguera R, Navarro S, Påhlman S, Versteeg R, Ora I, Gisselsson D, Lindgren D and Axelson H: snoRNPs regulate telomerase activity in neuroblastoma and are associated with poor prognosis. Transl Oncol. 6:447–457. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Montanaro L, Brigotti M, Clohessy J, Barbieri S, Ceccarelli C, Santini D, Taffurelli M, Calienni M, Teruya-Feldstein J, Trerè D, et al: Dyskerin expression influences the level of ribosomal RNA pseudo-uridylation and telomerase RNA component in human breast cancer. J Pathol. 210:10–18. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar : PubMed/NCBI

31 

Karin M, Cao Y, Greten FR and Li ZW: NF-kappaB in cancer: From innocent bystander to major culprit. Nat Rev Cancer. 2:301–310. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Uhlik M, Good L, Xiao G, Harhaj EW, Zandi E, Karin M and Sun SC: NF-kappaB-inducing kinase and IkappaB kinase participate in human T-cell leukemia virus I Tax-mediated NF-kappaB activation. J Biol Chem. 273:21132–21136. 1998. View Article : Google Scholar : PubMed/NCBI

33 

Kumar A, Takada Y, Boriek AM and Aggarwal BB: Nuclear factor-kappaB: Its role in health and disease. J Mol Med (Berl). 82:434–448. 2004. View Article : Google Scholar : PubMed/NCBI

34 

Kim A, Kim MJ, Yang Y, Kim JW, Yeom YI and Lim JS: Suppression of NF-kappaB activity by NDRG2 expression attenuates the invasive potential of highly malignant tumor cells. Carcinogenesis. 30:927–936. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Kessenbrock K, Plaks V and Werb Z: Matrix metalloproteinases: Regulators of the tumor microenvironment. Cell. 141:52–67. 2010. View Article : Google Scholar : PubMed/NCBI

36 

Alawi F and Lee MN: DKC1 is a direct and conserved transcriptional target of c-MYC. Biochem Biophys Res Commun. 362:893–898. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhang M, Pan Y, Jiang R, Hou P, Shan H, Chen F, Jiang T, Bai J and Zheng J: DKC1 serves as a potential prognostic biomarker for human clear cell renal cell carcinoma and promotes its proliferation, migration and invasion via the NF‑κB pathway. Oncol Rep 40: 968-978, 2018.
APA
Zhang, M., Pan, Y., Jiang, R., Hou, P., Shan, H., Chen, F. ... Zheng, J. (2018). DKC1 serves as a potential prognostic biomarker for human clear cell renal cell carcinoma and promotes its proliferation, migration and invasion via the NF‑κB pathway. Oncology Reports, 40, 968-978. https://doi.org/10.3892/or.2018.6484
MLA
Zhang, M., Pan, Y., Jiang, R., Hou, P., Shan, H., Chen, F., Jiang, T., Bai, J., Zheng, J."DKC1 serves as a potential prognostic biomarker for human clear cell renal cell carcinoma and promotes its proliferation, migration and invasion via the NF‑κB pathway". Oncology Reports 40.2 (2018): 968-978.
Chicago
Zhang, M., Pan, Y., Jiang, R., Hou, P., Shan, H., Chen, F., Jiang, T., Bai, J., Zheng, J."DKC1 serves as a potential prognostic biomarker for human clear cell renal cell carcinoma and promotes its proliferation, migration and invasion via the NF‑κB pathway". Oncology Reports 40, no. 2 (2018): 968-978. https://doi.org/10.3892/or.2018.6484
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang M, Pan Y, Jiang R, Hou P, Shan H, Chen F, Jiang T, Bai J and Zheng J: DKC1 serves as a potential prognostic biomarker for human clear cell renal cell carcinoma and promotes its proliferation, migration and invasion via the NF‑κB pathway. Oncol Rep 40: 968-978, 2018.
APA
Zhang, M., Pan, Y., Jiang, R., Hou, P., Shan, H., Chen, F. ... Zheng, J. (2018). DKC1 serves as a potential prognostic biomarker for human clear cell renal cell carcinoma and promotes its proliferation, migration and invasion via the NF‑κB pathway. Oncology Reports, 40, 968-978. https://doi.org/10.3892/or.2018.6484
MLA
Zhang, M., Pan, Y., Jiang, R., Hou, P., Shan, H., Chen, F., Jiang, T., Bai, J., Zheng, J."DKC1 serves as a potential prognostic biomarker for human clear cell renal cell carcinoma and promotes its proliferation, migration and invasion via the NF‑κB pathway". Oncology Reports 40.2 (2018): 968-978.
Chicago
Zhang, M., Pan, Y., Jiang, R., Hou, P., Shan, H., Chen, F., Jiang, T., Bai, J., Zheng, J."DKC1 serves as a potential prognostic biomarker for human clear cell renal cell carcinoma and promotes its proliferation, migration and invasion via the NF‑κB pathway". Oncology Reports 40, no. 2 (2018): 968-978. https://doi.org/10.3892/or.2018.6484
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