Abstract
BackgroundRenal cell carcinoma (RCC) is one of the most common and lethal human urological malignancies around the world. Although many advancements in diagnostic and therapeutic strategies have been acquired, the prognosis of patients with metastatic RCC was poor. Thus, there is an urgent need to understand the molecular mechanism of RCC.MethodsThe quantitative real-time PCR (qRT-PCR) was used to detect the RNA expression of MOF in human RCC tissues and cell lines. The protein expression of MOF was analyzed with immunohistochemistry (IHC) and Western blot. To understand the regulatory mechanism of MOF in liver cancer, ChIP-qPCR assay and dual-luciferase assay were performed. Moreover, a series of in vivo and in vitro experiments were conducted to evaluate the effect of MOF on renal cell carcinoma progression.ResultsIn the present study, we found that Males absent on the first (MOF), a histone acetyltransferase involved in transcription activation, was significantly decreased in both RCC tissues and RCC cells compared to normal tissues and non-cancer cells. Moreover, MOF downregulation was associated with advanced histological grade, pathologic stage and distant metastasis of RCC patients. Ectopic expression of MOF could significantly attenuate cell proliferation and promote cell apoptosis. Besides, MOF overexpression also suppressed migration of RCC cells through inhibiting epithelial-mesenchymal transition (EMT). Importantly, the inhibition of tumor growth by MOF was further confirmed by in vivo studies. Mechanism dissection revealed that MOF could transcriptionally upregulate the expression of SIRT1, leading to attenuated STAT3 signaling, which was involved in cell proliferation and migration. Moreover, SIRT1 knockdown could restore the biological function induced by MOF overexpression.ConclusionsOur findings indicated that MOF serves as a tumor suppressor via regulation of SIRT1 in the development and progression of RCC, and MOF might be a potent biomarker for diagnosis and prognosis prediction of RCC patients.
Highlights
Renal cell carcinoma (RCC) is a malignant tumor arising from urinary tubular epithelial cells [1], accounting for more than 90% of tumors in human kidney
Results revealed that the expression of male absent on the first (MOF) was significantly downregulated in RCC tissues compared to adjacent normal tissues (Figure 1A), which was consistent with the result (Figure 1B) obtained from GEO database (GSE53757)
After analyzing the association between MOF expression and the clinicopathologic parameters, we found that low MOF expression level was significantly correlated with advanced histological grade, pathologic tumor stage and distant metastasis (Figure 1C)
Summary
Renal cell carcinoma (RCC) is a malignant tumor arising from urinary tubular epithelial cells [1], accounting for more than 90% of tumors in human kidney. Significant advances have been acquired in therapeutic strategies, including modified surgical techniques and improved systemic treatment with targeted agents, the prognosis of RCC is still far from satisfactory because of the tumor recurrence and metastasis [4]. Comprehension of the molecular mechanisms of RCC carcinogenesis and progression is essential for detecting diagnostic and therapeutic biomarkers. Renal cell carcinoma (RCC) is one of the most common and lethal human urological malignancies around the world. Many advancements in diagnostic and therapeutic strategies have been acquired, the prognosis of patients with metastatic RCC was poor. There is an urgent need to understand the molecular mechanism of RCC
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