Jumonji AT-rich interactive domain 1B(JARID1B) has been shown to be upregulated in many human cancers and plays a critical role in the development of cancers cells. Nevertheless, its functional role in colorectal cancer (CRC) progression is not fully understood. Herein, JARID1B expression levels were detected in clinical CRC samples by western blotting and qRT-PCR. DLD-1 cells with JARID1B knockdown or overexpression by stably transfected plasmids were used in vitro and in vivo study. Colony formation, 5-ethynyl-20-deoxyuridine (EdU) and Real Time Cellular Analysis (RTCA) assays were used to detect cell proliferation and growth. Transcriptome and CHIP assays were used to examine the molecular biology changes and molecular interaction in these cells. Nude mice was utilized to study the correlation of JARID1B and tumor growth in vivo. Here, we first observed that JARID1B was significantly upregulated in CRC tissue compared to adjacent normal tissues. In CRC patients, JARID1B high expression was positively relation with poor overall survival. Multivariate analyses revealed that high JARID1B expression was an independent predictive marker for the poor prognosis of CRC. In addition, we found that JARID1B promoted CRC cells proliferation by Wnt/β-catenin signaling pathway. Further studies demonstrated CDX2 as a downstream target of JARID1B, and our data demonstrated that CDX2 is crucial for JARID1B -mediated Wnt/β-catenin signaling pathway. Mechanistically, we demonstrated that JARID1B regulated CDX2 expression through demethylation of H3K4me3. CDX2 inhibited by JARID1B-derived H3K4me3 methylation promoted cells proliferation of CRC via Wnt/β-catenin signaling pathway. Therefore, our studies provided a novel insight into the role of JARID1B in CRC cells proliferation and potential new molecular target for treating CRC.

中文翻译：

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JARID1B 通过降低 CDX2 水平促进结直肠癌增殖和 Wnt/β-catenin 信号传导

Jumonji AT 丰富的交互域 1B(JARID1B) 已被证明在许多人类癌症中被上调，并在癌细胞的发展中发挥关键作用。然而，其在结直肠癌 (CRC) 进展中的功能作用尚不完全清楚。在此，通过蛋白质印迹和 qRT-PCR 在临床 CRC 样本中检测 JARID1B 表达水平。在体外和体内研究中使用了 JARID1B 敲低或通过稳定转染质粒过表达的 DLD-1 细胞。集落形成、5-乙炔基-20-脱氧尿苷 (EdU) 和实时细胞分析 (RTCA) 检测用于检测细胞增殖和生长。转录组和 CHIP 测定用于检查这些细胞中的分子生物学变化和分子相互作用。裸鼠被用来研究 JARID1B 与体内肿瘤生长的相关性。这里，我们首先观察到 JARID1B 在 CRC 组织中与相邻的正常组织相比显着上调。在 CRC 患者中，JARID1B 高表达与较差的总生存率呈正相关。多变量分析表明，高 JARID1B 表达是 CRC 预后不良的独立预测标志物。此外，我们发现 JARID1B 通过 Wnt/β-catenin 信号通路促进 CRC 细胞增殖。进一步的研究表明 CDX2 是 JARID1B 的下游靶标，我们的数据表明 CDX2 对 JARID1B 介导的 Wnt/β-catenin 信号通路至关重要。从机制上讲，我们证明 JARID1B 通过 H3K4me3 的去甲基化调节 CDX2 表达。JARID1B衍生的H3K4me3甲基化抑制CDX2通过Wnt/β-catenin信号通路促进CRC细胞增殖。所以，