Long non-coding RNA FENDRR inhibits the stemenss of colorectal cancer cells through directly binding to Sox2 RNA

长链非编码RNA FENDRR通过直接结合Sox2 RNA抑制结直肠癌细胞的干细胞

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作者:Xin Zhao, Jincheng Wu, Yongwen Li, Feng Ye, Chunyue Wang

Abstract

Cancer stem cells (CSCs) contribute to malignant features. Long non-coding RNA (LncRNA) FENDRR has been shown to regulate tumor proliferation, migration, and invasion. However, the effects of FENDRR on the CSC-like traits of colorectal cancer cells remain to be elucidated. Here, we identified that lncRNA FENDRR level was remarkably lower in spheres formed by colorectal cancer cells compared to that in parental cancer cells. Further functional experiments showed that FENDRR overexpression attenuated the CSC-like traits of colorectal cancer spheres, while FENDRR knockdown conferred the CSC-like traits for colorectal cancer cells, as characterized by the alteration of ALDH activity, sphere-formation ability, and expression of stemness markers (Oct4, Sox2, and KLF4). RNA-RNA interaction in vitro analysis combined with mRNA stability assay revealed that lncRNA FENDRR directly interacted with Sox2 mRNA 3'UTR, reduced its mRNA stability and thus inhibited Sox2 expression. In addition, lncRNA FENDRR-mediated effects on the CSC-like traits of colorectal cancer cells depended on Sox2 expression. This work suggests that lncRNA FENDRR can block the CSC-like traits in colorectal cancer cells through directly interacting with Sox2 mRNA 3'UTR.

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