Xu Jing, Wu Guanghai, Zhao Yongjie, Han Youkui, Zhang Shuai, Li Chao, Zhang Judong
Department of General Surgery, Tianjin Union Medical Center, Jieyuan Road 190, Hongqiao District, Tianjin, 300121, PR China.
J Cancer. 2020 Sep 23;11(22):6623-6632. doi: 10.7150/jca.46562. eCollection 2020.
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.
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。
