Potential Diagnostic Marker For Ovarian Cancer: The Involvement Of Histone Acetyltransferase Human MOF

Ovarian cancer is the most common cause of cancer death from gynecologic tumors [9]. Due to difficulties in early detection, most ovarian cancers are diagnosed at an advanced stage. Research efforts has been found various biomarkers of diagnostic and prognostic of ovarian cancer including the potential tumor hypoxic markers HIF1‐α (hypoxia inducible factor‐1‐α) and its regulated genes such as vascular endothelial growth factor (VEGF), carbonate anhydrate IX (CA9) and stanniocalcin1(STC1)[1‐3], but they are not specific and sensitive enough to accurately predict the survival of ovarian cancer patients [4,5].Recent studies indicate that epigenetic alterations play an important role in carcinogenesis, and global histone modifications as predictors of cancer recurrence in various tumor entities has begun to study [6]. Although the role of hMOF and its corresponding modification in transcription regulation is not completely understood, abnormal expression of the hMOF and its corresponding modification of H4K16have been found in certain primary cancer tissues. The expression behavior of hMOF in the different primary cancers was observed different. No matter what kind of situation, hMOF protein expression tightly correlated with acetylation of histone H4K16. Above observations strongly suggest that histone acetyltransferase hMOF and its corresponding histone acetylation of H4K16might be involved in the certain tumorigenesis. However, only little is known about the role of hMOF and its corresponding modification in ovarian carcinomas.Here we first examined the hMOF mRNA and protein expression levels in primary ovarian carcinomas by qPCR, western blotting and immunohistochemistry. In support, we also examined the hMOF‐regulated HLA complex P5(HCP5) mRNA expression levels in ovarian cancer tissues.This study included the following aspects:1. Reverse transcription PCR (RT‐PCR)2. Western blotting3. Immunohistochemical staining4. RNAi treatment and DNA microarray5. Chromatin Immunoprecipitation (ChIP)The main result of this study as follows:Analysis of performed mRNA expression of47samples by RT‐PCR revealed down‐regulation of hMOF mRNA in81%of patients, whereas only13%of patients showed up‐regulation. Quantitative real time RT‐PCR was used to further validate the frequent down‐regulation of hMOF expression in primary ovarian cancer tissues. As expected, analysis of performed hMOF expression of57samples revealed significant (>2‐fold decreased) downregulation of hMOF mRNA in65%of patients, and less than2‐fold reduction of hMOF was observed in10.5%of patients. In support, we show that the expression of hMOF‐regulated HCP5was also downregulated in>87%of hMOF‐decreased patients.Conclusion:hMOF and its regulated gene HCP5are frequently downregulated in human ovarian cancer, suggesting hMOF might be involved in the pathogenesis of ovarian cancer.Creative feature of this research:Here we first examined the involvedment of hMOF expression and histone H4K16acetylation in primary ovarian cancer. The expression levels of hMOF‐target gene HCP5were also investigated.