AIMS RING1 and YY1-binding protein (RYBP) is an epigenetic regulator and plays crucial roles in embryonic development. The anti-tumor effect of RYBP has been reported in several cancers recently, but the role of RYBP in esophageal squamous cell carcinoma (ESCC) has not been fully elucidated. The present study aimed to investigate the biological function and the underlying molecular mechanisms of RYBP in ESCC. MATERIALS AND METHODS We detected the expression of RYBP in ESCC tissue microarrays (TMA) by immunohistochemistry. Cell proliferation was assessed by CCK8 and colony formation assays. Cell cycle was analyzed by flow cytometry. Gene expression was determined by transcriptome arrays, quantitative real-time PCR (qRT-PCR) and Western blot. Four-week-old male nude mice were used to evaluate the effect of RYBP in ESCC growth. KEY FINDINGS We found that RYBP was downregulated in ESCC compared with adjacent normal tissues. A high level of RYBP expression predicted a better outcome of ESCC patients. Furthermore, overexpression of RYBP inhibited ESCC growth both in vitro and in vivo. Transcriptome arrays and functional studies showed that RYBP decreased the expression of genes related to cell cycles, especially CDC6 and CDC45, which were essential to initiate the DNA replication and G1-S transition. SIGNIFICANCE Taken together, our study suggests that RYBP suppresses ESCC proliferation by downregulating CDC6 and CDC45, thus inhibiting the G1-S transition.

中文翻译：

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RYBP通过在G1-S相变过程中下调CDC6和CDC45抑制食管鳞状细胞癌的增殖。

AIMS RING1和YY1结合蛋白（RYBP）是一种表观遗传调控因子，在胚胎发育中起着至关重要的作用。RYBP的抗肿瘤作用最近在几种癌症中都有报道，但是尚未完全阐明RYBP在食管鳞状细胞癌（ESCC）中的作用。本研究旨在探讨RYBP在ESCC中的生物学功能和潜在的分子机制。材料与方法我们通过免疫组织化学检测了RYBP在ESCC组织微阵列（TMA）中的表达。通过CCK8和集落形成测定法评估细胞增殖。通过流式细胞术分析细胞周期。基因表达通过转录组阵列，实时定量PCR（qRT-PCR）和蛋白质印迹法确定。使用四周大的雄性裸鼠评估RYBP对ESCC生长的影响。主要发现我们发现，与邻近的正常组织相比，ESCC中的RYBP被下调。RYBP的高表达预示了ESCC患者的预后更好。此外，RYBP的过表达在体外和体内均抑制ESCC生长。转录组阵列和功能研究表明，RYBP降低了与细胞周期相关的基因的表达，尤其是CDC6和CDC45，这对于启动DNA复制和G1-S过渡至关重要。意义综上所述，我们的研究表明RYBP通过下调CDC6和CDC45从而抑制G1-S过渡来抑制ESCC增殖。RYBP的过表达在体外和体内均抑制ESCC的生长。转录组阵列和功能研究表明，RYBP降低了与细胞周期相关的基因的表达，尤其是CDC6和CDC45，这对于启动DNA复制和G1-S过渡至关重要。意义综上所述，我们的研究表明RYBP通过下调CDC6和CDC45从而抑制G1-S过渡来抑制ESCC增殖。RYBP的过表达在体外和体内均抑制ESCC的生长。转录组阵列和功能研究表明，RYBP降低了与细胞周期相关的基因的表达，尤其是CDC6和CDC45，这对于启动DNA复制和G1-S过渡至关重要。意义综上所述，我们的研究表明RYBP通过下调CDC6和CDC45从而抑制G1-S过渡来抑制ESCC增殖。