Circular RNA circ-ITCH inhibits bladder cancer progression by sponging miR-17/miR-224 and regulating p21, PTEN expression

Abstract

BackgroundCirc-ITCH is a circRNA generated from several exons of itchy E3 ubiquitin protein ligase (ITCH) and tumor suppressor served as a sponge for certain miRNAs targeting their parental transcripts of ITCH. However, the role of circ-ITCH in bladder cancer (BCa) was not reported. In the present study, we investigated the role of circ-ITCH in BCa.MethodsQuantitative real-time PCR was used to detect the expression of circ-ITCH and survival analysis was adopted to explore the association between circ-ITCH expression and the prognosis of BCa. BCa cells were stably transfected with lentivirus approach and cell proliferation, migration, invasion, cell cycle and cell apoptosis, as well as tumorigenesis in nude mice were performed to assess the effect of circ-ITCH in BCa. Biotin-coupled probe pull down assay, Biotin-coupled miRNA capture, Fluorescence in situ hybridization and Luciferase reporter assay were conducted to confirm the relationship between the circ-ITCH and the microRNA.ResultsIn the present study, we found that circ-ITCH, is down-regulated in BCa tissues and cell lines. BCa patients with low circ-ITCH expression had shortened survival. Enforced- expression of circ-ITCH inhibited cells proliferation, migration, invasion and metastasis both in vitro and in vivo. Mechanistically, we demonstrated that circ-ITCH up-regulates the expression of miR-17 and miR-224 target gene p21 and PTEN through ‘sponging’ miR-17 and miR-224, which suppressed the aggressive biological behaviors of BCa.Conclusionscirc-ITCH acts as a tumor suppressor by a novel circ-ITCH/miR-17, miR-224/p21, PTEN axis, which may provide a potential biomarker and therapeutic target for the management of BCa.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0771-7) contains supplementary material, which is available to authorized users.

Circular RNA CCDC66 targets DCX to regulate cell proliferation and migration by sponging miR‐488‐3p in Hirschsprung's disease

“…At present, increasing studies demonstrate that circRNAs take part in complicated physiological and pathological processes, and serve as miRNA sponges to regulate related target genes (Hansen, Kjems, & Damgaard, ; X. Meng et al, ). Bladder cancer could be inhibited by circ‐ITCH via sponging miR‐17/miR‐224 (Yang et al, ). HSCR, a congenital intestinal disease, is caused by defects in the migration of ENCCs.…”

CircMTO1 inhibits liver fibrosis via regulation of miR‐17‐5p and Smad7

“…Recent studies have demonstrated that circRNAs could act as miRNA sponges that regulate gene expression. 23 To determine whether circMTO1 interacts with miRNAs, RIP experiment was performed. Results of RIP showed that circMTO1 was significantly enhanced in the Ago2 group in comparison with the control ( Figure 5A).…”

Decreased expression of hsa_circ_0137287 predicts aggressive clinicopathologic characteristics in papillary thyroid carcinoma

“…Due to the application of next‐generation sequencing and bioinformatics, circRNAs were now discovered to be widely expressed in cells, exceeding the abundance of the linear mRNAs . circRNAs have now become a new star in RNA research field, as recent reports revealed their critical roles in various biological processes . They can mediate gene expression by sponging miRNAs and RBPs as well as regulating transcription and alternative splicing.…”

“…5,10,20 circRNAs have now become a new star in RNA research field, as recent reports revealed their critical roles in various biological processes. 12,[21][22][23][24] They can mediate gene expression by sponging miRNAs and RBPs as well as regulating transcription and alternative splicing. Notably, recent evidence also shows that some circRNAs can be translated into proteins, 25,26 which expands the definition and function of circRNA.…”