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

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.

Keywords: Colorectal cancer; Long noncoding RNAs; MicroRNAs; Migration; Proliferation.