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[Transcription Factor SAP30 Is Involved in the Activation of NETO2 Gene Expression in Clear Cell Renal Cell
A V Snezhkina1, K M Nyushko2, A R Zaretsky3,4
1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
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.
Insights
Clear cell renal cell carcinoma (ccRCC) involves increased NETO2 gene expression, primarily from isoform 1. This study identifies SAP30 as a key transcription factor linked to NETO2 upregulation in ccRCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is a prevalent cancer with increasing incidence and high mortality.
- Understanding the molecular drivers of ccRCC is critical for developing improved diagnostic and therapeutic strategies.
- Previous research identified elevated NETO2 gene expression in ccRCC.
Purpose of the Study:
- To investigate the specific NETO2 gene isoform responsible for increased expression in ccRCC.
- To elucidate the molecular mechanisms underlying NETO2 gene activation in ccRCC.
- To identify potential transcription factors regulating NETO2 expression in ccRCC.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) data using CrossHub software.
- Quantitative PCR to measure mRNA levels of candidate genes in ccRCC samples.
- Correlation analysis between NETO2 expression and identified transcription factors.
Main Results:
- NETO2 isoform 1 (NM_018092.4) significantly contributes to the gene's upregulation in ccRCC.
- Methylation was not found to be a major factor in NETO2 mRNA level increase.
- SAP30 transcription factor expression was significantly increased in ccRCC and positively correlated with NETO2 expression.
Conclusions:
- NETO2 upregulation in ccRCC is primarily driven by isoform 1.
- Increased expression of the SAP30 transcription factor is a probable mechanism for NETO2 activation in ccRCC.
- SAP30 represents a potential therapeutic target for ccRCC.
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