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

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

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

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