LncRNA WWC2-AS1 functions AS a novel competing endogenous RNA in the regulation of FGF2 expression by sponging miR-16 in radiation-induced intestinal fibrosis

• Main Authors: Ju-Mei Zhou, Rong Liang, Su-Yu Zhu, Hui Wang, Min Zou, Wei-Jing Zou, Shao-Lin Nie
• Format: Article
• Language: English
• Published: BMC 2019-07-01
• Series: BMC Cancer
• Subjects: WWC2-AS1; Radiation-induced intestinal fibrosis; ceRNA; miR-16; FGF2
• Online Access: http://link.springer.com/article/10.1186/s12885-019-5754-6

Abstract Background Recently, long non-coding RNAs (lncRNAs) were considered as important gene expression regulators involving various biological processes. In this study, we explored the role of lncRNAs in the pathogenesis of radiation-induced intestinal fibrosis (RIF). Methods LncRNAs were screened by microarray (Human LncRNA Array v3.0, Arraystar, Inc.) and the differentially expressed lncRNAs in RIF and non-RIF were analyzed by bioinformatics methods. The expression of WWC2-AS1/miR-16/FGF2 axis was compared on mRNA and protein level between human intestinal CCD-18Co fibroblasts cell lines and subepithelial SEMFs in response to radiation treatment. The significance of WWC2-AS1 in regulating FGF2 associated proliferation, migration, invasion and fibrosis of CCD-18Co and SEMFs by exposure to radiation was analyzed by shRNA (WWC2-AS1 shRNA) knock-down of endogenous WWC2-AS1. Results WWC2-AS1 and FGF2 level was significantly higher while miR-16 was down-regulated in radiation-treated intestinal tissues. WWC2-AS1 more potently boosted FGF2 expression via reducing miR-16, and WWC2-AS1 shRNA remarkably inhibited FGF2 associated proliferation, migration, invasion and fibrosis of radiation treatment in vitro, further demonstrating physical interaction between miR-16 and WWC2-AS1 in radiation-induced fibrosis progress. Conclusions WWC2-AS1 was highly expressed in RIF, may function as a ceRNA in the regulation of FGF2 by binding miR-16. Targeting WWC2-AS1 thus may benefit radiation-induced fibrosis treatment.