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

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.

KEYWORDS:

• Long non-coding rna
• sox2
• cancer stem cell
• mRNA stability
• RNA–RNA interaction

Contributors’ statement

Feng Ye and Chunyue Wang designed the research. Xin Zhao, Jincheng Wu, and Yongwen Li performed the research. Xin Zhao and Jincheng Wu wrote the manuscript.

Data Availability Statement

All data generated or analyzed during this study are included in this published article.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (No: 81772332); Jiangsu medical innovation team project (No: CXTDB2017004) in analysis and interpretation of data;Jiangsu medical innovation team project [CXTDB2017004];