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长链非编码RNA DSCAM-AS1通过miR-137/Notch1轴促进结肠癌细胞增殖和迁移。

Long Noncoding RNA DSCAM-AS1 Facilitates Colorectal Cancer Cell Proliferation and Migration via miR-137/Notch1 Axis.

作者信息

Xu Jing, Wu Guanghai, Zhao Yongjie, Han Youkui, Zhang Shuai, Li Chao, Zhang Judong

机构信息

Department of General Surgery, Tianjin Union Medical Center, Jieyuan Road 190, Hongqiao District, Tianjin, 300121, PR China.

出版信息

J Cancer. 2020 Sep 23;11(22):6623-6632. doi: 10.7150/jca.46562. eCollection 2020.

Abstract

Growing evidences demonstrate that long noncoding RNAs (lncRNAs) participate in various cancers including colorectal cancer (CRC). In the current study, we found that the expression of DSCAM-AS1 in CRC tissues and cell lines was significantly upregulated, and was positively correlated with metastasis status and advanced stage of CRC. In addition, Kaplan-Meier assays also indicated that the expression of DSCAM-AS1 was correlated with poor prognosis in patients with CRC. Silence of DSCAM-AS1 inhibited proliferation and migration of CRC cells. Subcellular fractionation and FISH analyses suggested that DSCAM-AS1 was majorly distributed in cytoplasm of HT29 and LOVO cells. Thus, DSCAM-AS1 might act as a competing endogenous RNA (ceRNA). Subsequently, RT-qPCR results displayed that the expression of miR-137 in CRC tissues was relatively lower than that in the neighboring normal tissues. The interaction between miR-137 and DSCAM-AS1 was demonstrated by luciferase reporter assay. Functionally, miR-137 reversed the pro-proliferation and -metastasis effect of DSCAM-AS1 on CRC cells. Collectively, DSCAM-AS1 promotes CRC progression via sponging miR-137. MiR-137 can suppress the expression of Notch-1, a novel signaling regulating cell proliferation and EMT, by working on the 3'UTR of Notch-1. At last, Notch-1 overexpression or miR-137 inhibition could restore the DSCAM-AS1 silencing-mediated repressive function on cell proliferation and migration. The above data suggested that, DSCAM-AS1 may contribute to CRC cell proliferation and migration by targeting miR-137/Notch-1 axis.

摘要

越来越多的证据表明,长链非编码RNA(lncRNA)参与包括结直肠癌(CRC)在内的多种癌症。在本研究中,我们发现DSCAM-AS1在CRC组织和细胞系中的表达显著上调,且与CRC的转移状态和晚期阶段呈正相关。此外,Kaplan-Meier分析还表明,DSCAM-AS1的表达与CRC患者的不良预后相关。沉默DSCAM-AS1可抑制CRC细胞的增殖和迁移。亚细胞分级分离和FISH分析表明,DSCAM-AS1主要分布在HT29和LOVO细胞的细胞质中。因此,DSCAM-AS1可能作为一种竞争性内源性RNA(ceRNA)发挥作用。随后,RT-qPCR结果显示,CRC组织中miR-137的表达相对低于邻近正常组织。荧光素酶报告基因检测证实了miR-137与DSCAM-AS1之间的相互作用。在功能上,miR-137可逆转DSCAM-AS1对CRC细胞的促增殖和促转移作用。总体而言,DSCAM-AS1通过海绵吸附miR-137促进CRC进展。miR-137可通过作用于Notch-1的3'UTR抑制Notch-1的表达,Notch-1是一种调节细胞增殖和EMT的新型信号通路。最后,Notch-1过表达或miR-137抑制可恢复DSCAM-AS1沉默介导的对细胞增殖和迁移的抑制作用。上述数据表明,DSCAM-AS1可能通过靶向miR-137/Notch-1轴促进CRC细胞的增殖和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31b3/7545673/ff7a6b966148/jcav11p6623g001.jpg

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