Epigenetic change in kidney tumor: downregulation of histone acetyltransferase MYST1 in human renal cell carcinoma

Abstract

BackgroundMYST1 (also known as hMOF), a member of the MYST family of histone acetyltransferases (HATs) as an epigenetic mark of active genes, is mainly responsible for histone H4K16 acetylation in the cells. Recent studies have shown that the abnormal gene expression of hMOF is involved in certain primary cancers. Here we examined the involvement of hMOF expression and histone H4K16 acetylation in primary renal cell carcinoma (RCC). Simultaneously, we investigated the correlation between the expression of hMOF and clear cell RCC (ccRCC) biomarker carbohydrase IX (CA9) in RCC.Materials and methodsThe frozen RCC tissues and RCC cell lines as materials, the reverse transcription polymerase chain reaction (RT-PCR), western blotting and immunohistochemical staining approaches were used.ResultsRT-PCR results indicate that hMOF gene expression levels frequently downregulated in 90.5% of patients (19/21) with RCC. The reduction of hMOF protein in both RCC tissues and RCC cell lines is tightly correlated with acetylation of histone H4K16. In addition, overexpression of CA9 was detected in 100% of ccRCC patients (21/21). However, transient transfection of hMOF in ccRCC 786–0 cells did not affect both the gene and protein expression of CA9.ConclusionhMOF as an acetyltransferase of H4K16 might be involved in the pathogenesis of kidney cancer, and this epigenetic changes might be a new CA9-independent RCC diagnostic maker.

Correlation of low expression of hMOF with clinicopathological features of colorectal carcinoma, gastric cancer and renal cell carcinoma

“…We previously found downregulation of hMOF (91% of patients, 19/21) in RCC, resulting in decreased hMOF protein, and this reduction is tightly correlated with histone H4K16 acetylation (21). To further confirm our results and to evaluate the relationship between hMOF expression and clinicopathological parameters, we measured hMOF mRNA using qPCR in 47 patients diagnosed with RCC.…”

“…Here we first examined the hMOF mRNA and protein expression levels in primary CRC and gastric cancer by quantitative PCR (qPCR) and western blotting (WB). In addition, we recently reported the hMOF HAT is frequently downregulated in ovarian cancer and RCC (29,21), here we further analyzed the relationship between low-expression of hMOF and clinicopathological features in RCC. Cancer patients underwent radical tumor surgery at the First Hospital of Jilin University.…”

“…The expression patterns of hMOF in different primary cancers varied. Frequent downregulation of hMOF expression was found in breast cancer, medulloblastoma and RCC (20,21). On the contrary, hMOF was overexpressed in non-small cell lung carcinoma tissues (22,23).…”

Expression of hMOF in different ovarian tissues and its effects on ovarian cancer prognosis

“…In recent years, the effects of hMOF on the occurrence and development of malignant tumors has been a hot area of study in international academia. Previous studies indicated that hMOF is frequently downregulated in primary breast carcinoma and medulloblastoma (19), human renal cell (20), and colorectal carcinoma, and gastric cancer (23). However, the expression of hMOF was reportedly much higher in NSCLC compared to corresponding normal tissues, and hMOF promoted the proliferation, metastasis and adhesion of NSCLC cell lines (21).…”

“…Furthermore, they found that hMOF protein expression is a prognostic marker for medulloblastoma, with patients harboring tumors with a low hMOF expression having a significantly worse survival (19). In a study on human renal cell carcinoma, Wang et al found that the expression of hMOF in cancer tissues was significantly lower than that in adjacent kidney tissues (20). However, hMOF was more frequently found to be highly expressed in non-small cell lung cancer (NSCLC) than corresponding normal tissues, and hMOF promoted the proliferation, metastasis and adhesion of NSCLC cell lines (21).…”