Circ-ITCH inhibits bladder cancer progression through miR-184/FOXO3 axis

Objective: This study aimed to explore the role of circ-ITCH in the progression of bladder cancer (BCa).

Methods: Kaplan-Meier analysis was performed to evaluate the prognostic significance of miR-184 in bladder cancer. Clustering analysis compared miR-184 expression levels across various BCa cell lines. Cell Counting Kit-8 (CCK-8) and transwell assays were used to assess cell proliferation and migration. Dual-luciferase reporter assays were employed to examine the regulatory relationship among circ-ITCH, miR-184, and FOXO3. Western blot analysis was conducted to investigate the post-transcriptional regulation of the circ-ITCH/miR-184/FOXO3 axis.

Results: The study demonstrated a correlation between elevated miR-184 expression and poor prognosis in bladder cancer. Compared to SV-HUC, a normal bladder tissue cell line, most BCa cell lines exhibited increased miR-184 expression. Additionally, miR-184 was found to promote BCa cell progression. Importantly, circ-ITCH was identified as a natural sponge for miR-184 in BCa. Overexpression of circ-ITCH in BCa significantly reduced miR-184 expression, thereby inhibiting cell proliferation and migration. Moreover, FOXO3, a target of miR-184, is regulated by circ-ITCH. The suppression of FOXO3 by miR-184 was counteracted by circ-ITCH, which diminished the tumor-promoting effects of miR-184.

Conclusions: This study underscores the pivotal role of the circ-ITCH/miR-184/FOXO3 axis in regulating BCa cell proliferation and migration. It introduces a potential therapeutic target for bladder cancer, suggesting that strategies like circ-ITCH overexpression and miR-184 inhibition could offer promising treatment options.