Biopolym. Cell. 2014; 30(3):229-233.
Biomedicine
PPM1M and PRICKLE2 are potential tumor suppressor genes in human clear-cell renal cell carcinoma
1Rudenko E. E., 1Gerashchenko G. V., 1Lapska Y. V., 2Vozianov S. O., 2Zgonnyk Y. M., 1Kashuba V. I.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. State Institution «Institute of Urology of NAMS of Ukraine»
    9-a, Yu. Kotsubyns'koho Str., Kyiv, Ukraine, 04053

Abstract

Aim. To investigate the expression levels of PPM1M and PRICKLE2 in clear-cell renal cell carcinomas (ccRCC) and propose a mechanism leading to the expression changes in tumor. Methods. Analysis of GEO data, quantitative PCR (Q-PCR), bisulfite sequencing, methylation-specific PCR, deletion search. Results. We found that the PRICKLE2 expression was down-regulated in 83 % of samples. Decreased expression of PPM1M was shown in 33.3 % of ccRCC samples. The promoters of PPM1M and PRICKLE2 were not methylated, and no deletions were found in their sequences. Conclusions. Our data suggest that PRICKLE2 and PPM1M might be candidates for the tumor suppressor genes in ccRCC.
Keywords: renal cell carcinoma, genetic and epigenetic regulation, quantitative real time PCR, deletion, methylation status

References

[1] Bhat S. Role of surgery in advanced/metastatic renal cell carcinoma. Indian J Urol. 2010;26(2):167-76.
[2] Dmitriev AA, Rudenko EE, Kudryavtseva AV, Krasnov GS, Gordiyuk VV, Melnikova NV, Stakhovsky EO, Kononenko OA, Pavlova LS, Kondratieva TT, Alekseev BY, Braga EA, Senchenko VN, Kashuba VI. Epigenetic alterations of chromosome 3 revealed by NotI-microarrays in clear cell renal cell carcinoma. BioMed Research International. 2014 (2014), Article ID 735292, 9 p.
[3] Henmi T, Amano K, Nagaura Y, Matsumoto K, Echigo S, Tamura S, Kobayashi T. A mechanism for the suppression of interleukin-1-induced nuclear factor kappaB activation by protein phosphatase 2Ceta-2. Biochem J. 2009;423(1):71-8.
[4] Katoh M. WNT/PCP signaling pathway and human cancer (review). Oncol Rep. 2005;14(6):1583-8.
[5] Senchenko VN, Kisseljova NP, Ivanova TA, Dmitriev AA, Krasnov GS, Kudryavtseva AV, Panasenko GV, Tsitrin EB, Lerman MI, Kisseljov FL, Kashuba VI, Zabarovsky ER. Novel tumor suppressor candidates on chromosome 3 revealed by NotI-microarrays in cervical cancer. Epigenetics. 2013;8(4).
[6] Dmitriev AA, Kashuba VI, Haraldson K, Senchenko VN, Pavlova TV, Kudryavtseva AV, Anedchenko EA, Krasnov GS, Pronina IV, Loginov VI, Kondratieva TT, Kazubskaya TP, Braga EA, Yenamandra SP, Ignatjev I, Ernberg I, Klein G, Lerman MI, Zabarovsky ER. Genetic and epigenetic analysis of non-small cell lung cancer with NotI-microarrays. Epigenetics. 2012;7(5):502-13.
[7] Kashuba V, Dmitriev AA, Krasnov GS, Pavlova T, Ignatjev I, Gordiyuk VV, Gerashchenko AV, Braga EA, Yenamandra SP, Lerman M, Senchenko VN, Zabarovsky E. NotI Microarrays: Novel Epigenetic Markers for Early Detection and Prognosis of High Grade Serous Ovarian Cancer. Int J Mol Sci. 2012;13(10):13352-77.
[8] Gerashchenko GV, Bogatyrova OO, Rudenko EE, Kondratov AG, Gordiyuk VV, Zgonnyk YM, Vozianov OF, Pavlova TV, Zabarovsky ER, Rynditch AV, Kashuba VI. Genetic and epigenetic changes of NKIRAS1 gene in human renal cell carcinomas. Exp Oncol. 2010;32(2):71-5.
[9] Jung M, Ramankulov A, Roigas J, Johannsen M, Ringsdorf M, Kristiansen G, Jung K. In search of suitable reference genes for gene expression studies of human renal cell carcinoma by real-time PCR. BMC Mol Biol. 2007;8:47.
[10] Rudenko EE, Gerashchenko GV, Lapska YV, Bogatyrova OO, Vozianov SO, Zgonnyk YM, Kashuba VI. Genetic and epigenetic changes of GPX1 and GPX3 in human clear-cell renal cell carcinoma. Biopolym Cell. 2013;29(5):395–401.
[11] Daulat AM, Luu O, Sing A, Zhang L, Wrana JL, McNeill H, Winklbauer R, Angers S. Mink1 regulates ?-catenin-independent Wnt signaling via Prickle phosphorylation. Mol Cell Biol. 2012;32(1):173-85.