Circular RNA ITCH suppresses metastasis of gastric cancer via regulating miR-199a-5p/Klotho axis. Issue 5 (19th March 2021)

• Record Type: Journal Article
• Authors: Wang, Yan; Wang, Huiting; Zheng, Ruiqi; Wu, Peipei; Sun, Zixuan; Chen, Jingyan; Zhang, Leilei; Zhang, Chenxiao; Qian, Hui; Jiang, Jiajia; Xu, Wenrong
• Is Part Of: Cell cycle. Volume 20:Issue 5/6(2021)
• Page Start: 522
• Page End: 536
• Publication Date: 2021-03-19
• Subjects: Circ-ITCH -- gastric cancer -- miR-199a-5p -- klotho -- biomarker; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2021.1878327
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: Circular RNAs (circRNAs) are considered as a new regulatory factor in growth, metastasis and therapeutic resistance of human cancers. But the clinical significance and underlying mechanism of circular RNA ITCH (circ-ITCH) in gastric cancer (GC) remain unknown. In the present study, we found that circ-ITCH was down-regulated in GC cell lines, GC tissues and their serum-derived exosomes. The level of circ-ITCH was related to invasion depth. Functional assays showed that circ-ITCH overexpression inhibited the proliferation, migration, invasion and epithelial mesenchymal transition (EMT) of GC cells, whereas circ-ITCH knockdown appeared an opposite effect. Bioinformatic analysis and luciferase reporter assay confirmed that circ-ITCH acted as miR-199a-5p sponge and increased the level of Klotho. The expression level of miR-199-5p was up-regulated in GC tissues and negatively correlated with that of circ-ITCH. MiR-199a-5p mimics reversed the effects on inhibiting metastasis induced by circ-ITCH overexpression and decreased the level of Klotho in GC cells. Our findings indicate that circ-ITCH suppresses metastasis of GC by acting as the sponge of miR-199a-5p and increasing Klotho expression, which serves as a potential biomarker and targets for the diagnosis and therapy of GC. Abbreviations: CircRNAs: circular RNAs; GC: gastric cancer; circ-ITCH: circular RNA Itchy E3 ubiquitin protein ligase; ceRNA: competitive endogenous RNA; EMT: Epithelial–mesenchymal transition; siRNA: Small interfering RNA; TEM: transmission electron microscope; NTA: nanoparticle tracking analysis.