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Vol 52(2018) N 3 p. 385-392; DOI 10.1134/S0026893318020152 Full Text

A.V. Snezhkina1, K.M. Nyushko2, A.R. Zaretsky3,4, D.A. Shagin3, A.F. Sadritdinova1,2, M.S. Fedorova1, Z.G. Guvatova1, I.S. Abramov1, E.A. Pudova1, B.Y. Alekseev2, A.A. Dmitriev1, A.V. Kudryavtseva1,2*

Transcription Factor SAP30 Is Involved in the Activation of NETO2 Gene Expression in Clear Cell Renal Cell Carcinoma

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, 125284 Russia
3Pirogov Russian National Research Medical University, Moscow, 117997 Russia
4Evrogen Lab LLC, Moscow, 117437 Russia

*rhizamoeba@mail.ru
Received - 2016-12-09; Accepted - 2017-03-03

Clear cell renal cell carcinoma (ccRCC) is a common oncourological disease with a high mortality level. The incidence of this type of cancer is constantly increasing, while molecular mechanisms involved in the disease initiation and progression remain far from being fully understood. A problem of the search for novel markers is crucial for improvement of diagnosis and therapy of ccRCC. We have previously found that the disease is characterized by increased expression of the NETO2 gene. In the present study, we showed that isoform 1 (NM_018092.4) makes the main contribution to the upregulation of this gene. Using original CrossHub software, "The Cancer Genome Atlas" (TCGA) project data were analyzed to identify possible mechanisms of NETO2 gene activation in ccRCC. The absence of significant contribution of methylation to the increase of mRNA level of the gene was observed. At the same time, a number of genes encoding transcription factors, which could potentially regulate the expression of NETO2 in ccRCC, were identified. Three such genes (MYCBP, JMY, and SAP30) were selected for the further analysis of their mRNA levels in a set of ccRCC samples with quantitative PCR. We showed a significant increase in mRNA level of one of the examined genes, SAP30, and revealed its positive correlation with NETO2 gene expression. Thus, upregulation of NETO2 gene is first stipulated by the isoform 1 (NM_018092.4), and the probable mechanism of its activation is associated with the increased expression of SAP30 transcription factor.

clear cell renal cell carcinoma, NETO2, oncogene, SAP30, transcription factors, qPCR



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