Circular RNA ITCH has inhibitory effect on ESCC by suppressing the Wnt/β-catenin pathway

Abstract

Circular RNAs with exonic sequences represent a special form of non-coding RNAs, discovered by analyzing a handful of transcribed genes. It has been observed that circular RNAs function as microRNA sponges. In the present study, we investigated whether the expression of circular RNAs is altered during the development of esophageal squamous cell carcinoma (ESCC). Using a TaqMan-based reverse transcriptase polymerase chain reaction assay, the relationship between cir-ITCH and ESCC was analyzed in a total of 684 ESCC and paired adjacent non-tumor tissue samples from eastern and southern China. We found that cir-ITCH expression was usually low in ESCC compared to the peritumoral tissue. The functional relevance of cir-ITCH was further examined by biochemical assays. As sponge of miR-7, miR-17, and miR-214, cir-ITCH might increase the level of ITCH. ITCH hyper expression promotes ubiquitination and degradation of phosphorylated Dvl2, thereby inhibiting the Wnt/β-catenin pathway. These results indicate that cir-ITCH may have an inhibitory effect on ESCC by regulating the Wnt pathway.

The emerging role and clinical implication of human exonic circular RNA

“…It was shown that cir-ITCH expression is typically downregulated in esophageal squamous cell carcinoma. 44 This circular RNA could increase the level of ITCH by acting as miRNA sponge. In another study, cir-ITCH was shown to play an inhibitory role in colorectal cancer by regulating the Wnt/b-catenin pathway.…”

Roles of the circular RNA circ-Foxo3 in breast cancer progression

“…For example, the circRNA circ-ITCH contains binding sites for miR-7, miR-17, and miR-214 and represses the activity of these microRNAs. 1 To serve as a sponge, however, a circular RNA has to contain many microRNA binding sites and be expressed at sufficiently high levels in cytoplasm. The majority of circRNAs may not be in this category and their functions remain uncertain.…”

Identification of circular RNAs hsa_circ_0044235 in peripheral blood as novel biomarkers for rheumatoid arthritis

“…Recent studies have revealed that abnormal circRNAs are associated with several human diseases, such as atherosclerotic vascular disease, cancer and autoimmune disease 22, 23, 24, 25, 26. Many dysregulated expression circRNAs are demonstrated to associate with RA 16, 17.…”

“…Previous studies have shown that miRNAs and lncRNA are involved in the pathogenesis of RA and can be used as biomarkers for the diagnosis of RA 8, 9, 10, 11. Increasing evidence reveals that circRNAs are used widely in various physiological and pathological conditions, such as atherosclerotic vascular diseases, neurological disorders, prion infection and cancer 12, 13, 14, 15. However, little is known about the roles of circRNAs in human RA.…”