Abstract
BackgroundRecently, 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).MethodsLncRNAs 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.ResultsWWC2-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.ConclusionsWWC2-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.
Highlights
Long non-coding RNAs were considered as important gene expression regulators involving various biological processes
WWC2-AS1 is closely related to fibroblast growth factor 2 (FGF2) signaling in radiation-induced intestinal fibrosis (RIF) By gene ontology (GO) analysis, we found multiple genes near long non-coding RNAs (lncRNAs) that might encode key factors of the fibrosis signaling pathway, such as FGF2
To confirm whether FGF2 screened from lncRNA chips is related to WWC2-AS1 in RIF, we assess the FGF2 level using RT-qPCR and Western blot, and found expression of FGF2 in RIF was significantly higher than control tissues (Figs. 2a and 2b), indicating FGF2 in RIF group was up-regulated
Summary
Long non-coding RNAs (lncRNAs) were considered as important gene expression regulators involving various biological processes. We explored the role of lncRNAs in the pathogenesis of radiation-induced intestinal fibrosis (RIF). Radiation-induced intestinal fibrosis (RIF) is a common complication in patients with abdominal and pelvic malignancies who have received radiotherapy. The multifunctional cytokine fibroblast growth factor 2 (FGF2) orchestrates an intricate signaling network to modulate radiation-induced fibrosis. FGF2 exacts its role in radiation-induced fibrosis through enhancing interstitial cell proliferation and stimulating trans-differentiation of fibroblasts into myofibroblasts [4, 5] partially through its ability to induce the epithelial-mesenchymal transition (EMT) [6, 7]. The EMT has been shown to be of critical importance in damage repair and organ fibrosis [8,9,10].
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have