JARID1B promotes colorectal cancer proliferation and Wnt/β-catenin signaling via decreasing CDX2 level.
JARID1B promotes colorectal cancer proliferation and Wnt/β-catenin signaling via decreasing CDX2 level.
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JARID1B通过降低CDX2水平促进结直肠癌的增殖和Wnt/β-catenin信号传导。
DOI：
10.1186/s12964-020-00660-4
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发表时间：
2020-10-27
期刊：
影响因子：
--
通讯作者：
Liu F
中科院分区：
文献类型：
--
作者：
Huang D;Xiao F;Hao H;Hua F;Luo Z;Huang Z;Li Q;Chen S;Cheng X;Zhang X;Fang W;Hu X;Liu F
Jumonji AT丰富的相互作用结构域1B（JARID 1B）已被证明在许多人类癌症中上调，并在癌细胞的发展中起着关键作用。然而，其在结直肠癌（CRC）进展中的功能作用尚未完全了解。在此，通过蛋白质印迹和qRT-PCR检测临床CRC样品中的JARID 1B表达水平。在体外和体内研究中使用通过稳定转染的质粒敲低或过表达JARID 1B的DLD-1细胞。采用集落形成、5-乙炔基-20-脱氧尿苷（EdU）和真实的时间细胞分析（RTCA）检测细胞增殖和生长。采用转录组和芯片检测技术检测细胞的分子生物学变化和分子间的相互作用。利用裸鼠研究JARID 1B与体内肿瘤生长的相关性。在这里，我们首先观察到，与邻近的正常组织相比，JARID 1B在CRC组织中显著上调。在结直肠癌患者中，JARID 1B高表达与总生存率低呈正相关。多因素分析显示，JARID 1B高表达是CRC预后不良的独立预测指标。另外，我们发现JARID 1B通过Wnt/β-catenin信号通路促进结直肠癌细胞增殖。进一步的研究表明CDX 2是JARID 1B的下游靶点，我们的数据表明CDX 2在JARID 1B介导的Wnt/β-catenin信号通路中至关重要。从机制上讲，我们证明了JARID 1B通过H3 K4 me 3的去甲基化来调节CDX 2的表达。JARID 1B H3 K4 me 3甲基化抑制CDX 2通过Wnt/β-catenin信号通路促进结直肠癌细胞增殖。因此，我们的研究为JARID 1B在CRC细胞增殖中的作用和治疗CRC的潜在新分子靶点提供了新的见解。视频摘要在线版本包含补充材料，可通过10. 1186/s12964-020-00660-4获取。
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. Video abstract The online version contains supplementary material available at 10.1186/s12964-020-00660-4.
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影响因子：
5.7
作者：
Kuo KT;Huang WC;Bamodu OA;Lee WH;Wang CH;Hsiao M;Wang LS;Yeh CT
通讯作者：
Yeh CT
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影响因子：
4.5
作者：
Gacek-Matthews A;Berger H;Sasaki T;Wittstein K;Gruber C;Lewis ZA;Strauss J
通讯作者：
Strauss J
影响因子：
--
作者：
Lu W;Liu S;Li B;Xie Y;Adhiambo C;Yang Q;Ballard BR;Nakayama KI;Matusik RJ;Chen Z
通讯作者：
Chen Z
影响因子：
2.9
作者：
Tóth C;Sükösd F;Valicsek E;Herpel E;Schirmacher P;Tiszlavicz L
通讯作者：
Tiszlavicz L
影响因子：
5.2
作者：
Catchpole, Steven;Spencer-Dene, Bradley;Taylor-Papadimitriou, Joyce
通讯作者：
Taylor-Papadimitriou, Joyce