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
Authors: Campagna, Roberto; Cecati, Monia; Pozzi, Valentina; Fumarola, Stefania; Pompei, Veronica; Milanese, Giulio; Galosi, Andrea Benedetto; Sartini, Davide; Emanuelli, Monica
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 ceRCC 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-1 beta) and transforming growth.factor beta 1 (TOF-1 beta) 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-1 beta 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-1 beta gene expression levels. TOF-beta 1 up-regulation could be responsible for the high levels of NNMT observed in ccRCC. Targeting TOF1 beta 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.
Physiological Study on Association between Nicotinamide N-Methyltransferase Gene Polymorphisms and Hyperlipidemia
BIOMED RESEARCH INTERNATIONAL
Authors: Zhu, Xiao-Juan; Lin, Ya-Jun; Chen, Wei; Wang, Ya-Hui; Qiu, Li-Qiang; Cai, Can-Xin; Xiong, Qun; Chen, Fei; Chen, Li-Hui; Zhou, Qiong; Li, Jiang-Hua
Abstract
Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide. Our previous works indicate that NNMT is involved in the body mass index and energy metabolism, and recently the association between a SNP (rs694539) of NNMT and a variety of cardiovascular diseases was reported. At present, more than 200 NNMT single nucleotide polymorphisms (SNPs) have been identified in the databases of the human genome projects; however, the association between rs694539 variation and hyperlipidemia has not been reported yet, and whether there are any SNPs in NNMT significantly associated with hyperlipidemia is still unclear. In this paper, we selected 19 SNPs in NNMT as the tagSNPs using Haploview software (Haploview 4.2) first and then performed a case-control study to observe the association between these tagSNPs and hyperlipidemia and finally applied physiological approaches to explore the possible mechanisms through which the NNMT polymorphism induces hyperlipidemia. The results show that a SNP (rs1941404) in NNMT is significantly associated with hyperlipidemia, and the influence of rs1941404 variation on the resting energy expenditure may be the possible mechanism for rs1941404 variation to induce hyperlipidemia.