CircDUSP22 Attenuates the Ferroptosis of Prostate Cancer Cells via miR-18a-5p/SLC7A11/GPX4 Signaling
Authors: Jiang Hua , Zhang He , Jiang Songsong 
Published: July 2024

Background:

According to current worldwide cancer data, Prostate Cancer (PC)
ranks as the second most common type of cancer and is the fifth leading cause of cancer-related
mortality among men worldwide. PC in China has the 10th highest number of new cases and the
13th highest fatality rate, both of which show an ongoing annual increase. One of the significant
challenges with prostate cancer is the difficulty in early detection, often resulting in diagnosis at
intermediate or late stages, complicating treatment. Although hormonal therapy is initially successful
in controlling the progression of prostate cancer, almost all tumors that respond to hormones
eventually transform into Castration-resistant Prostate Cancer (CRPC) within 18-24
months of hormonal therapy. This poses clinical difficulties due to an absence of successful therapeutic
approaches. Therefore, understanding the fundamental mechanisms of prostate cancer
development, identifying effective therapeutic targets, and discovering reliable molecular biomarkers
are crucial objectives.

Methods:

CircRNA expression in plasma was assessed in 4 samples obtained from patients with
Benign Prostatic Hyperplasia (BPH), and PC was detected through microarray probes. Statistical
analysis of the expression of circDUSP22 and clinicopathological features was conducted. The
investigation of target genes was conducted using luciferase reporter assays and bioinformatics
analysis. The expression levels of circDUSP22, miR-18a-5p, and Solute Carrier Family 7 member
11 (SLC7A11) were assessed using a quantitative Real-time Polymerase Chain Reaction
(qRT-PCR) assay. Cell invasion, migration, colony formation, and proliferation were evaluated
using Transwell, wound healing, colony formation, and CCK-8 assays, respectively. RNA Immunoprecipitation
(RIP) and dual-luciferase reporter assays were used to examine the connections
among circDUSP22, miR-18a-5p, and SLC7A11. The impact of circDUSP22 on the expression
of ferroptosis-related proteins, specifically SLC7A11, as well as its effects on Fe2+ and
ROS were also examined.

Results:

In both plasma samples and PCa cell lines, there was a substantial elevation of
circDUSP22 and SLC7A11 expression and a decline in miR-18a-5p expression. Suppression of
circDUSP22 significantly impeded the migration, invasion, and proliferation of PC cells in vitro.
The target gene of miR-18a-5p, SLC7A11, was found to be upregulated as an effect of
circDUSP22's competitive binding to miR-18a-5p. Cellular experiments demonstrated that interference
with circDUSP22 expression in DU145 and PC-3 cells led to increased ferroptosis and
decreased SLC7A11 expression. The modulation of prostate cancer cell proliferation was reversed
by either overexpressing SLC7A11 or inhibiting miR-18a-5p in response to the silencing
of circDUSP22.

Conclusion:

The circDUSP22 has been found to have a substantial effect on the development of
ferroptosis in PC. It has been observed to influence the formation and evolution of this disorder
by affecting the miR-18a-5p/SLC7A11 signaling pathway.