JARID1B promotes colorectal cancer proliferation and Wnt/β-catenin signaling via decreasing CDX2 level

Cell Communication and Signaling

Zhaoxia Huang¹  Sha Chen²  Xiaoyun Hu³  Haibin Hao³  Qing Li⁴  Da Huang⁵  Zhenzhong Luo⁶  Fuzhou Hua⁶  Fan Xiao⁶  Xinyue Zhang⁷  Fanrong Liu⁷  Xiuzhi Cheng⁷  Weilan Fang⁷ 

[1] Center for Education Evaluation, Nanchang Normal University, Nanchang, China;Department of Anesthesiology, Second Affiliated Hospital of Nanchang University, Nanchang, China;Department of Pathology, Second Affiliated Hospital of Nanchang University, Nanchang, China;Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China;Department of Pathology, Second Affiliated Hospital of Nanchang University, Nanchang, China;Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China;Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China;Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China;Department of Anesthesiology, Second Affiliated Hospital of Nanchang University, Nanchang, China;Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China;Department of Pathology, Second Affiliated Hospital of Nanchang University, Nanchang, China;

关键词: Colorectal cancer;    Cell proliferation;    JARID1B;    CDX2;    H3K4me3;    Wnt/β-catenin;   

DOI  :  10.1186/s12964-020-00660-4

来源: Springer

【 摘 要 】

BackgroundJumonji 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.MethodsHerein, 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.ResultsHere, 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.ConclusionsCDX2 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.7iDCCN6fi_Z-Myd1SxMdsEVideo abstractGraphical abstract

【 授权许可】

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