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Silencing of long noncoding RNA P53RRA suppressed ferroptosis in prostate cancer by activating the AKT signaling pathway

ABSTRACT: Background: Investigations regarding the function of ferroptosis in prostate cancer (PCa) progression are still rare. Therefore, this study revealed the function of long noncoding RNA P53RRA (P53RRA)-mediated ferroptosis in PCa. Methods: The levels of P53RRA, TFR1, IREB2, SLC7A11, and GPX4 in DU145 cells were examined by quantitative real-time PCR and Western blot. Besides, cell proliferation was tested by Cell Counting Kit-8; GSH, MDA, and reactive oxygen species (ROS) levels were examined using the corresponding kits, flow cytometry, or fluorescence. Additionally, P53RRA silenced DU145 cells were treated with an AKT inhibitor to confirm the role of the AKT signaling pathway in P53RRA-mediated ferroptosis. Then, transcriptome RNA sequencing (RNA-seq) obtained the mRNA expression profiling. Results: P53RRA was down-expressed in PCa cells compared with normal human prostate epithelial cells. Silencing of P53RRA decreased the levels of TFR1 and IREB2 while promoted the expression of SLC7A11 and GPX4. Knockdown of P53RRA promoted the proliferation ability and GSH level while decreased ROS and MDA levels. Additionally, the bioinformatics analysis showed that P53RRA silencing enriched in phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway causes the aberrantly expressed mRNAs. Besides, P53RRA silencing induced the phosphorylation of AKT. Interestingly, AZD5363 treatment increased TFR1 and IREB2 levels inhibited by P53RRA silence and decreased SLC7A11 and GPX4 levels stimulated by P53RRA silence. Besides, AZD5363 administration partly reversed the silencing of P53RRA-mediated proliferation promotion, increased the level of GSH, and inhibition on MDA/ROS levels. Conclusions: Silencing of P53RRA suppressed ferroptosis by activating the AKT signaling pathway to modulate the development of prostate cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268705 | GEO | 2025/05/30

REPOSITORIES: GEO

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Silencing of long noncoding RNA P53RRA suppressed ferroptosis in prostate cancer by activating the AKT signaling pathway

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