Abstract
BackgroundOur study aimed to explore the expression and the biological role of lysine-specific demethylase 2A (KDM2A) in clear cell renal cell carcinoma (ccRCC).MethodsIn vitro, KDM2A expression was measured by qRT-PCR and western blot. A total of 50 patients with ccRCC were included, and KDM2A expression in ccRCC tissues was assessed by qRT-PCR and immunohistochemistry. The effects of KDM2A expression on cell biological behavior were examined by cell counting kit-8 assay, transwell assay and flow cytometry, respectively. The prognostic value of KDM2A in ccRCC was evaluated by Kaplan–Meier method.ResultsThe KDM2A expression was significantly upregulated in ccRCC cell line (P < 0.05). Compared with para cancer tissues, ccRCC samples showed a higher KMD2A mRNA level and a larger proportion of high KDM2A expression (all P < 0.05). High KDM2A mRNA expression was more likely to occur in ccRCC tissues with tumor size > 7 cm (P = 0.005) and T3-T4 stage (P = 0.047). Knockdown of KDM2A significantly suppressed the proliferation and invasion, and promoted the apoptosis of ccRCC cells (all P < 0.05). Moreover, Kaplan–Meier survival analysis revealed that higher level of KDM2A expression in ccRCC patients was associated with lower survival rate (P = 0.004).ConclusionsOur findings demonstrated a vital role of KDM2A in the pathogenesis of ccRCC, which provides a new perspective to understand the underlying molecular mechanisms in ccRCC.
Highlights
Our study aimed to explore the expression and the biological role of lysine-specific demethylase 2A (KDM2A) in clear cell renal cell carcinoma
We analyzed the correlations of Lysine-specific demethylase 2A (KDM2A) mRNA and protein expression with clinical features in clear cell renal cell carcinoma (ccRCC) and found that the high expression of KDM2A mRNA was more likely to occur in ccRCC tissues with tumor size > 7 cm (P = 0.005) and T3-T4 stage (P = 0.047) (Table 3)
The occurrence and development of ccRCC is a complicated multi-step biological process, which may involve the instability of the genome, the gradual accumulation of gene mutations, epigenetic mechanism alterations, and Emerging studies have shown that the level of KDM2A expression is up-regulated in a variety of tumor cells and affects the biological behavior of tumor cells
Summary
Our study aimed to explore the expression and the biological role of lysine-specific demethylase 2A (KDM2A) in clear cell renal cell carcinoma (ccRCC). Kidney cancer is a common malignancy of urinary system, whereas renal cell carcinoma (RCC) is the most common kidney neoplasm and contains a cluster of heterogeneous tumors which originate from the renal tubular epithelial cells [1, 2]. Clear cell renal cell carcinoma (ccRCC) is the most frequent subtype of RCC, which nearly accounts for about 75%. Covalent histone modifications play a critical part in the regulation of chromatin dynamics and functions [5]. Through the methylation of different histone sites, gene expressions can be regulated by influencing the activation and inhibition of transcription [6]. KDM2A has a complex and tissue-specific role in tumorigenesis and tumor progression. Its expression pattern and biological function in ccRCC have not yet been elucidated
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