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.

Abstract. Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and has been described as one of the deadliest of cancers affecting the genitourinary tract. Tropomyosin is a two-stranded α-helical coiled coil protein found in cell cytoskeletons. One of its isoforms, tropomyosin-1 (TPM1) has been reported as a novel tumor-suppressor gene and is downregulated in many solid tumors. However the expression level and function of TPM1 in RCC have not yet been determined. In the present study, we evaluated the TPM1-4 mRNA and TPM1 protein levels in RCC tissue samples. TPM1-overexpressing OSRC-2 and 786-O cell lines were also used to investigate the impact of TPM1 on RCC cells. We found that TPM1 was significantly and specifically downregulated in the RCC tissues. TPM1 expression was associated with tumor size, smoking status, Fuhrman grade and the prognosis of RCC patients. After TPM1 transfection, the migratory and invasive abilities of the OSRC-2 and 786-O cell lines were both reduced when compared to the control groups. Meanwhile, apoptosis was also enhanced in these two RCC cell lines following TPM1 transfection. Taken together, TPM1 exhibits characteristics of a tumor-suppressor gene while being overexpressed in RCC cell lines. IntroductionRenal cell carcinoma (RCC), which originates from renal tubular epithelial cells, accounts for 80-85% of all cases of kidney cancer, and is responsible for ~2-3% of all malignant diseases in adults (1). The overall 5-year survival of RCC is as low as 20-25%, and the most important factor in the selection of the appropriate therapy for RCC patients is the presence of metastases (2).Tropomyosin (TPM) is an important component of microfilaments, a cytoskeleton structure, and is mainly involved in the contraction of skeletal and smooth muscle cells or maintaining the stability of the cytoskeleton in non-muscular cells (3). Four tropomyosin genes, TPM1, TPM2, TPM3 and TPM4, have been confirmed in mammals including humans. More than 20 isoforms can be produced through alternative splicing. All of these homologous isoforms fold into two parallel, linear chains of spiral α-helices (4). These TPM proteins are involved in the regulation of many benign myopathies, such as myasthenia gravis and familial hypertrophic cardiomyopathy (5). Additionally, other studies have discovered that TPM1 plays an important role as a tumor-suppressor gene (TSG) in tumor occurrence and progression (6,7). Recently, evidence indicates that TPM1 could be a novel target gene of microRNA-21 which was found to be upregulated in many different solid tumors, including RCC (8). However, whether or not TPM1 serves as a tumor-suppressor gene in RCC and is selectively downregulated during RCC development has not been determined. Therefore, in the present study, we investigated the expression level of TPM1 in a set of RCC tissue samples and further evaluated its tumor-suppressing activities in two RCC cell lines (786-O and OSRC-2). Materials and methodsTissue samples. Ninety-eight tissue samples in...