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Vol. 64 No. 7: Issue 7

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Involvement of transforming growth factor beta 1 in the transcriptional regulation of nicotinamide N-methyltransferase in clear cell renal cell carcinoma

https://doi.org/10.14715/cmb/2018.64.7.9
Roberto Campagna
Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy
Monia Cecati
Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy
Valentina Pozzi
New York-Marche Structural Biology Center (NY-MaSBiC), Polytechnic University of Marche, Ancona, Italy
Stefania Fumarola
Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy
Veronica Pompei
Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy
Giulio Milanese
Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy
Andrea Benedetto Galosi
Davide Sartini
Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy
Monica Emanuelli
Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy

Corresponding Author(s) : Davide Sartini

davide_sartini@libero.it

Cellular and Molecular Biology, Vol. 64 No. 7: Issue 7

Abstract

Renal cell carcinoma (RCC) is the most common tumor of the kidney and its major histologic subtype is clear cell RCC (ccRCC). About 30% of diagnosed ccRCCs already have metastasis. Traditionally, localized ccRCC is treated with nephrectomy but the relapse rate is 30%. Thus, the discovery of effective biomarkers for early detection, as well as the identification of new targets for molecular-based therapy of ccRCC are urgently required. In this study, we focused on molecules that could modulate the trascription of the enzyme nicotinamide N-methyltransferase (NNMT) that is known to be up-regulated in ccRCC. Signal transducer and activator of transcription 3 (STAT3), interleukin 6 (IL-6), hepatocyte nuclear factor 1 beta (HNF-1β) and transforming growth factor beta 1 (TGF-β1) expression levels were determined in tumor and non tumor samples obtained from 30 patients with ccRCC, using Real-Time PCR. Results obtained showed that TGF-β1 is significantly (p<0.05) overexpressed in tumor compared with normal tissue samples of ccRCC patients. Conversely, we did not find any statistically significant difference concerning STAT3, IL-6, HNF-1β gene expression levels. TGF-β1 up-regulation could be responsible for the high levels of NNMT observed in ccRCC. Targeting TGF-β1 could improve the outcome of ccRCC patients due to its role in epithelial-mesenchymal transition (EMT), that is known to be associated with a worse overall survival (OS) in this neoplasm.

Keywords

Renal cell carcinoma NNMT Biomarker TGF-β1 Transcription factor.
Campagna, R., Cecati, M., Pozzi, V., Fumarola, S., Pompei, V., Milanese, G., Galosi, A. B., Sartini, D., & Emanuelli, M. (2018). Involvement of transforming growth factor beta 1 in the transcriptional regulation of nicotinamide N-methyltransferase in clear cell renal cell carcinoma. Cellular and Molecular Biology, 64(7), 51–55. https://doi.org/10.14715/cmb/2018.64.7.9
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