NSD2 circular RNA promotes metastasis of colorectal cancer by targeting miR-199b-5p-mediated DDR1 and JAG1 signalling
NSD2 circular RNA promotes metastasis of colorectal cancer by targeting miR-199b-5p-mediated DDR1 and JAG1 signalling
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NSD2环状RNA通过靶向miR-199b-5p介导的DDR1和JAG1信号促进结直肠癌的转移
DOI：
10.1002/path.5238
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发表时间：
2019-05-01
影响因子：
7.3
通讯作者：
Li, Jian-Ming
中科院分区：
文献类型：
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作者：
Chen, Liang-Yan;Zhi, Zheng;Li, Jian-Ming
肝转移是结直肠癌（CRC）患者死亡的主要原因。在这里，我们通过使用RNA（转录组）测序在CRC肝转移的小鼠模型中搜索CRC转移相关的环状RNA。我们鉴定了一种新的保守的环状RNA，circ-NSD 2，作为CRC转移的启动子。Circ-NSD 2表达在CRC组织中升高，并且在CRC患者的晚期或转移性肿瘤中显著增加。功能获得和功能丧失实验表明，circ-NSD 2在体外和体内促进CRC的迁移和转移。在机制上，circ-NSD 2充当肿瘤抑制因子miR-199 b-5 p的海绵，并激活DDR 1（盘状结构域受体酪氨酸激酶1）和JAG 1（Jagged 1）基因，这协同有助于CRC细胞的细胞-基质相互作用、迁移和转移。综上所述，我们的研究结果强调了circ-NSD 2的一种新的致癌功能，并揭示了circ-NSD 2/miR-199 b-5 p/DDR 1/JAG 1轴在CRC转移中的关键机制，这可能成为CRC患者抗转移治疗的预后因素和治疗靶点。版权所有（c）2019大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
Liver metastasis is the main cause of death in patients with colorectal cancer (CRC). Here, we searched for CRC metastasis-associated circular RNA in a mouse model of liver metastasis of CRC by using RNA (transcriptome)-sequencing. We identified a novel and conserved circular RNA, circ-NSD2, functioning as a promoter of CRC metastasis. Circ-NSD2 expression was elevated in CRC tissues and was markedly increased in advanced stages or metastatic tumours of CRC patients. Gain-of-function and loss-of-function experiments demonstrated that circ-NSD2 promoted migration and metastasis of CRC in vitro and in vivo. Mechanistically, circ-NSD2 acted as a sponge for the tumour suppressor miR-199b-5p and activated DDR1 (discoidin domain receptor tyrosine kinase 1) and JAG1 (Jagged 1) genes, which synergistically helped with cell-matrix interaction, migration and metastasis of CRC cells. Taken together, our findings highlight a novel oncogenic function of circ-NSD2 and uncover a key mechanism for the circ-NSD2/miR-199b-5p/DDR1/JAG1 axis in CRC metastasis, which may serve as a prognostic factor and therapeutic target for antimetastatic therapy in CRC patients. Copyright (c) 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.