Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Prostate cancer (PCa) is one of the leading causes of male morbidity and mortality due to malignant disease?throughout the world. Recently, circRNAs have been considered as important regulators?in tumorigenesis related networks. Nevertheless, the?biological role and expression pattern of circRNA-ITCH (circ-ITCH) in prostate cancer are still not fully understood. Objectives: The purpose of the present study was to determine circ-ITCH expression?in prostate cancer tissues and cell lines and analyze its potential regulatory effects on the proliferation, apoptosis, migration and invasion of prostate cells in-vitro. Methods: The expression of circ-ITCH was detected in 6 pairs of PC tissues and adjacent?normal tissues (n = 6) as well as PC cell lines by quantitative real-time PCR. The function of circ-ITCH was assessed by?gain-of-function experiments. Cell proliferation and colony-forming efficiency were assessed using Cell Counting Kit-8 and plate cloning?assays, respectively. The migratory and invasive abilities were?examined via Wound Healing and Transwell assay and Annexin V-FITC/propidium iodide (PI) staining was used to assess apoptosis. Bioinformatic analysis in combination with dual-luciferase reporter analysis was performed to validate the regulatory?relationships between circ-ITCH, miR-106b-5p and SETD2. Results: Relative to the corresponding control group, circ-ITCH expression?was markedly decreased in prostate cancer tissues and cell lines. In-vitro, circ-ITCH overexpression inhibited cell?proliferation and clonogenicity and increased the number of apoptotic cells in prostate cancer. Moreover, circ-ITCH overexpression reduced cell migration and invasion abilities. The luciferase reporter assays confirmed that circ-ITCH was?the target of miR-106b-5p and miR-106b-5p targeted SETD2. circ-ITCH upregulation was?correlated with elevated SETD2 expression, which is in line with a miR-106b-5p–dependent pattern of regulation. Conclusion: These findings suggest that circ-ITCH can modulate malignant cell phenotypes (proliferation, apoptosis, migration and invasion) in PCa cells in-vitro through the?miR-106b-5p/SETD2 axis. There are only a limited number of tissue samples and?in-vitro experimental designs in our study and more experiments will be needed to further confirm these findings and reveal the biological significance.