It is worth mentioning that CA9 has been well described as
a diagnostic marker for clear cell renal carcinoma (ccRCC), especially by showing high expression in metastastic ccRCC (mccRCC) [31, 32]. Therefore, the inhibitor or regulatory proteins of hypoxic tumor-associated CA9 possesses the potential therapeutic possibility for those tumors in which CA9 is involved in perturbing the extra- or intra- tumoral acidification process. In our experiments, although the expression of VEGF and HIF1α which are hypoxia signature genes were not observed significant difference between ccRCC and normal tissues, Vorinostat datasheet overexpression of CA9 was observed in 100% of ccRCC cases and in both renal carcinoma cell lines.
Interestingly, in four different diagnostic RCCs, downregulation of hMOF was detected in all types of RCCs, but the overexpression of CA9 was only presented in ccRCC, suggesting that hMOF might AP26113 www.selleckchem.com/products/bmn-673.html be a new common diagnostic marker for human different diagnostic RCC. Although frequent downregulation of hMOF and overexpression of CA9 were detected in both RCC clinical tissues and RCC cell lines, non-correlation between hMOF and CA9 was found in RCC 786–0 cells, suggesting hMOF and its corresponding modifications might be a new CA9-independent RCC diagnosis biomarker. Although large series of clinical cases and analyses of overall survival need to be investigated, the molecular mechanism linking loss of hMOF expression to renal
cell carcinoma, especially mechanism of hMOF on renal cell carcinomas, will be an exciting avenue for further research. Conclusion In conclusion, hMOF as an acetyltransferase of H4K16 might be involved in the pathogenesis of renal cell carcinoma, and this epigenetic change might be a new CA9-independent RCC diagnostic marker. In addition, our results suggest that a novel molecular mechanism of hMOF might serve as a lead to new therapeutics target in human renal cell carcinoma. Acknowledgements This work was supported by National Natural Science Foundation of China (No. 31070668, JJ) and Research Fund 4-Aminobutyrate aminotransferase for the Doctoral Program of Higher Education of China (No. 20110061110020, JJ). References 1. Jin J, Cai Y, Li B, Conaway RC, Workman JL, Conaway JW, Kusch T: In and out: histone variant exchange in chromatin. Trends Biochem Sci 2005, 30:680–687.PubMedCrossRef 2. Berger SL: The complex languige of chromatin regulation during transcription. Nature 2007, 447:407–412.PubMedCrossRef 3. Bhaumik SR, Smith E, Shilatifard A: Covalent modifications of histones during development and disease pathogenesis. Nat Struct Mol Biol 2007, 14:1008–1016.PubMedCrossRef 4. Carrouzza MJ, Utley RT, Workman JL, Cote J: The divers functions of histone acetyltransferase complexes. Trends Genet 2003, 19:321–329.CrossRef 5.