| BMC Cancer | |
| Expression of methionine adenosyltransferase 2A in renal cell carcinomas and potential mechanism for kidney carcinogenesis | |
| Xuliang Wang3  Xiaoqiang Guo2  Wenshui Yu1  Cailing Li3  Yaoting Gui3  Zhiming Cai2  | |
| [1] Medical College, Shantou University, Shantou 515041, Guangdong, China | |
| [2] Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China | |
| [3] Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, Guangdong, China | |
| 关键词: Heme oxygenase-1; S-adenosylmethionine; Renal cell carcinomas; Methionine adenosyltransferase 2A; | |
| Others : 858960 DOI : 10.1186/1471-2407-14-196 |
|
| received in 2013-11-04, accepted in 2014-03-06, 发布年份 2014 | |
PDF
|
|
【 摘 要 】
Background
Methionine adenosyltransferase 2A (MAT2A) is an enzyme that catalyzes the formation of S-adenosylmethionine (SAMe) by joining methionine and ATP. SAMe is a methyl donor for transmethylation and has an important role for DNA and/or protein methylation. MAT2A is expressed widely in many tissues especially in kidney. Several studies have demonstrated that there are abnormal expressions of MAT2A in several kinds of cancers such as liver and colon cancers. But the relationship of MAT2A between renal cell carcinomas (RCC) is less understood.
Methods
The mRNA expression level of the MAT2A gene was determined in 24 RCC patients and 4 RCC cell lines, using real-time quantitative-polymerase chain reaction (RT-PCR). The MAT2A protein content was measured by western blotting and immunohistochemical analysis in 55 RCC patients. The mRNA levels of heme oxygenase-1 (HO-1) and cyclooxygenase-2 (COX-2) were also analysized in patients using RT-PCR. The correlations between the MAT2A and HO-1 as well as COX-2 were analyzed with nonparametric Spearman method.
Results
MAT2A transcript was significantly downregulated in cancer tissues compared to normal tissues (P < 0.05). Immunohistochemical analysis and western blotting indicated that level of MAT2A protein was decreased in cancer tissues. The statistical analysis reveals a negative correlation between MAT2A and HO-1 expression in RCC patients and cell lines (P < 0.01).
Conclusions
This study demonstrated that MAT2A was lower expression in cancer tissues, suggesting that it may be involved in the development of RCC. MAT2A is a transcriptional corepressor for HO-1 expression by supplying SAM for methyltransferases, which may be one of potential mechanism of MAT2A as tumor suppressor in kidney carcinogenesis.
【 授权许可】
2014 Wang et al.; licensee BioMed Central Ltd.
【 预 览 】
| Files | Size | Format | View |
|---|---|---|---|
| 20140724061102171.pdf | 1480KB | ||
| 55KB | Image | ||
| 65KB | Image | ||
| 195KB | Image | ||
| 63KB | Image |
【 图 表 】
【 参考文献 】
- [1]Rini BI, Campbell SC, Escudier B: Renal cell carcinoma. Lancet 2009, 373(9669):1119-1132.
- [2]Lopez-Beltran A, Carrasco JC, Cheng L, Scarpelli M, Kirkali Z, Montironi R: 2009 update on the classification of renal epithelial tumors in adults. Int J Urol 2009, 16(5):432-443.
- [3]Basu B, Eisen T: Perspectives in drug development for metastatic renal cell cancer. Target Oncol 2010, 5(2):139-156.
- [4]Ficarra V, Schips L, Guille F, Li G, De La Taille A, Prayer Galetti T, Cindolo L, Novara G, Zigeuner RE, Bratti E, Tostain J, Altieri V, Abbou CC, Artibani W, Patard JJ: Multiinstitutional European validation of the 2002 TNM staging system in conventional and papillary localized renal cell carcinoma. Cancer 2005, 104(5):968-974.
- [5]Mohammed A, Shergill I, Little B: Management of metastatic renal cell carcinoma: current trends. Expert Rev Mol Diagn 2009, 9(1):75-83.
- [6]Linehan WM, Srinivasan R, Schmidt LS: The genetic basis of kidney cancer: a metabolic disease. Nat Rev Urol 2010, 7(5):277-285.
- [7]Baldewijns MM, van Vlodrop IJ, Vermeulen PB, Soetekouw PM, van Engeland M, de Bruine AP: VHL and HIF signalling in renal cell carcinogenesis. J Pathol 2010, 221(2):125-138.
- [8]Sudarshan S, Karam JA, Brugarolas J, Thompson RH, Uzzo R, Rini B, Margulis V, Patard JJ, Escudier B, Linehan WM: Metabolism of kidney cancer: from the lab to clinical practice. Eur Urol 2013, 63(2):244-251.
- [9]Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD, Pan Y, Simon MC, Thompson CB, Gottlieb E: Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell 2005, 7(1):77-85.
- [10]Linehan WM, Rouault TA: Molecular pathways: Fumarate hydratase-deficient kidney cancer–targeting the Warburg effect in cancer. Clin Cancer Res 2013, 19(13):3345-3352.
- [11]Linehan WM, Ricketts CJ: The metabolic basis of kidney cancer. Semin Cancer Biol 2013, 23(1):46-55.
- [12]Locasale JW: Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat Rev Cancer 2013, 13(8):572-583.
- [13]Moore LE, Hung R, Karami S, Boffetta P, Berndt S, Hsu CC, Zaridze D, Janout V, Kollarova H, Bencko V, Navratilova M, Szeszenia-Dabrowska N, Mates D, Mukeria A, Holcatova I, Yeager M, Chanock S, Garcia-Closas M, Rothman N, Chow WH, Brennan P: Folate metabolism genes, vegetable intake and renal cancer risk in central Europe. Int J Cancer 2008, 122(8):1710-1715.
- [14]Gibson TM, Brennan P, Han S, Karami S, Zaridze D, Janout V, Kollarova H, Bencko V, Navratilova M, Szeszenia-Dabrowska N, Mates D, Slamova A, Pfeiffer RM, Stolzenberg-Solomon RZ, Mayne ST, Yeager M, Chanock S, Rothman N, Chow WH, Rosenberg PS, Boffetta P, Moore LE: Comprehensive evaluation of one-carbon metabolism pathway gene variants and renal cell cancer risk. PLoS One 2011, 6(10):e26165.
- [15]Greenberg AK, Rimal B, Felner K, Zafar S, Hung J, Eylers E, Phalan B, Zhang M, Goldberg JD, Crawford B, Rom WN, Naidich D, Merali S: S-adenosylmethionine as a biomarker for the early detection of lung cancer. Chest 2007, 132(4):1247-1252.
- [16]de Vogel S, Schneede J, Ueland PM, Vollset SE, Meyer K, Fredriksen A, Midttun O, Bjorge T, Kampman E, Bretthauer M, Hoff G: Biomarkers related to one-carbon metabolism as potential risk factors for distal colorectal adenomas. Cancer Epidemiol Biomarkers Prev 2011, 20(8):1726-1735.
- [17]Lu SC, Mato JM: Role of methionine adenosyltransferase and S-adenosylmethionine in alcohol-associated liver cancer. Alcohol 2005, 35(3):227-234.
- [18]Garcia-Trevijano ER, Latasa MU, Carretero MV, Berasain C, Mato JM, Avila MA: S-adenosylmethionine regulates MAT1A and MAT2A gene expression in cultured rat hepatocytes: a new role for S-adenosylmethionine in the maintenance of the differentiated status of the liver. FASEB J 2000, 14(15):2511-2518.
- [19]Hashimoto H, Vertino PM, Cheng X: Molecular coupling of DNA methylation and histone methylation. Epigenomics 2010, 2(5):657-669.
- [20]Cedar H, Bergman Y: Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet 2009, 10(5):295-304.
- [21]Ara AI, Xia M, Ramani K, Mato JM, Lu SC: S-adenosylmethionine inhibits lipopolysaccharide-induced gene expression via modulation of histone methylation. Hepatology 2008, 47(5):1655-1666.
- [22]Halim AB, LeGros L, Chamberlin ME, Geller A, Kotb M: Regulation of the human MAT2A gene encoding the catalytic alpha 2 subunit of methionine adenosyltransferase, MAT II: gene organization, promoter characterization, and identification of a site in the proximal promoter that is essential for its activity. J Biol Chem 2001, 276(13):9784-9791.
- [23]Liu Q, Liu L, Zhao Y, Zhang J, Wang D, Chen J, He Y, Wu J, Zhang Z, Liu Z: Hypoxia induces genomic DNA demethylation through the activation of HIF-1alpha and transcriptional upregulation of MAT2A in hepatoma cells. Mol Cancer Ther 2011, 10(6):1113-1123.
- [24]Zhang T, Zheng Z, Liu Y, Zhang J, Zhao Y, Liu Y, Zhu H, Zhao G, Liang J, Li Q, Xu H: Overexpression of methionine adenosyltransferase II alpha (MAT2A) in gastric cancer and induction of cell cycle arrest and apoptosis in SGC-7901 cells by shRNA-mediated silencing of MAT2A gene. Acta Histochem 2013, 115(1):48-55.
- [25]Chen H, Xia M, Lin M, Yang H, Kuhlenkamp J, Li T, Sodir NM, Chen YH, Josef-Lenz H, Laird PW, Clarke S, Mato JM, Lu SC: Role of methionine adenosyltransferase 2A and S-adenosylmethionine in mitogen-induced growth of human colon cancer cells. Gastroenterology 2007, 133(1):207-218.
- [26]Wang Q, Liu QY, Liu ZS, Qian Q, Sun Q, Pan DY: Inhibition of hepatocelluar carcinoma MAT2A and MAT2beta gene expressions by single and dual small interfering RNA. J Exp Clin Cancer Res 2008, 27:72. BioMed Central Full Text
- [27]Zhang W, Sviripa V, Chen X, Shi J, Yu T, Hamza A, Ward ND, Kril LM, Vander Kooi CW, Zhan CG, Evers BM, Watt DS, Liu C: Fluorinated N, N-dialkylaminostilbenes repress colon cancer by targeting methionine S-adenosyltransferase 2A. ACS Chem Biol 2013, 8(4):796-803.
- [28]Katoh Y, Ikura T, Hoshikawa Y, Tashiro S, Ito T, Ohta M, Kera Y, Noda T, Igarashi K: Methionine adenosyltransferase II serves as a transcriptional corepressor of Maf oncoprotein. Mol Cell 2011, 41(5):554-566.
- [29]Frezza C, Zheng L, Folger O, Rajagopalan KN, MacKenzie ED, Jerby L, Micaroni M, Chaneton B, Adam J, Hedley A, Kalna G, Tomlinson IP, Pollard PJ, Watson DG, Deberardinis RJ, Shlomi T, Ruppin E, Gottlieb E: Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature 2011, 477(7363):225-228.
- [30]Banerjee P, Basu A, Datta D, Gasser M, Waaga-Gasser AM, Pal S: The heme oxygenase-1 protein is overexpressed in human renal cancer cells following activation of the Ras-Raf-ERK pathway and mediates anti-apoptotic signal. J Biol Chem 2011, 286(38):33580-33590.
- [31]Banerjee P, Basu A, Wegiel B, Otterbein LE, Mizumura K, Gasser M, Waaga-Gasser AM, Choi AM, Pal S: Heme oxygenase-1 promotes survival of renal cancer cells through modulation of apoptosis- and autophagy-regulating molecules. J Biol Chem 2012, 287(38):32113-32123.
- [32]Miyata Y, Koga S, Kanda S, Nishikido M, Hayashi T, Kanetake H: Expression of cyclooxygenase-2 in renal cell carcinoma: correlation with tumor cell proliferation, apoptosis, angiogenesis, expression of matrix metalloproteinase-2, and survival. Clin Cancer Res 2003, 9(5):1741-1749.
- [33]Tuna B, Yorukoglu K, Gurel D, Mungan U, Kirkali Z: Significance of COX-2 expression in human renal cell carcinoma. Urology 2004, 64(6):1116-1120.
- [34]Igarashi K, Katoh Y: Metabolic aspects of epigenome: coupling of S-Adenosylmethionine synthesis and gene regulation on chromatin by SAMIT module. Subcell Biochem 2012, 61:105-118.
- [35]Kurdistani SK: Histone modifications in cancer biology and prognosis. Prog Drug Res 2011, 67:91-106.
PDF