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


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Abstract

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.

About the authors

A. V. Snezhkina

Engelhardt Institute of Molecular Biology

Email: rhizamoeba@mail.ru
Russian Federation, Moscow, 119991

K. M. Nyushko

National Medical Research Radiological Center

Email: rhizamoeba@mail.ru
Russian Federation, Moscow, 125284

A. R. Zaretsky

Pirogov Russian National Research Medical University; Evrogen Lab LLC

Email: rhizamoeba@mail.ru
Russian Federation, Moscow, 117997; Moscow, 117437

D. A. Shagin

Pirogov Russian National Research Medical University

Email: rhizamoeba@mail.ru
Russian Federation, Moscow, 117997

A. F. Sadritdinova

Engelhardt Institute of Molecular Biology; National Medical Research Radiological Center

Email: rhizamoeba@mail.ru
Russian Federation, Moscow, 119991; Moscow, 125284

M. S. Fedorova

Engelhardt Institute of Molecular Biology

Email: rhizamoeba@mail.ru
Russian Federation, Moscow, 119991

Z. G. Guvatova

Engelhardt Institute of Molecular Biology

Email: rhizamoeba@mail.ru
Russian Federation, Moscow, 119991

I. S. Abramov

Engelhardt Institute of Molecular Biology

Email: rhizamoeba@mail.ru
Russian Federation, Moscow, 119991

E. A. Pudova

Engelhardt Institute of Molecular Biology

Email: rhizamoeba@mail.ru
Russian Federation, Moscow, 119991

B. Y. Alekseev

National Medical Research Radiological Center

Email: rhizamoeba@mail.ru
Russian Federation, Moscow, 125284

A. A. Dmitriev

Engelhardt Institute of Molecular Biology

Email: rhizamoeba@mail.ru
Russian Federation, Moscow, 119991

A. V. Kudryavtseva

Engelhardt Institute of Molecular Biology; National Medical Research Radiological Center

Author for correspondence.
Email: rhizamoeba@mail.ru
Russian Federation, Moscow, 119991; Moscow, 125284

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