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Knockdown of FOXD3-AS1 inhibits the progression of prostate cancer by targeting miR-491-5p/PEG10

J Cancer Res Clin Oncol. 2025 Nov 25;151(12):329. doi: 10.1007/s00432-025-06364-x.

ABSTRACT

BACKGROUND: The lncRNA FOXD3-AS1 shows abnormal expression in various tumors, but its role in prostate cancer (PCa) remains unclear.

OBJECTIVE: This study sought to examine FOXD3-AS1 expression patterns in PCa and its molecular role in regulating PEG10 through miR-491-5p.

METHODS: The methodological approach involved the application of RT-qPCR to determine the expression profiles of FOXD3-AS1, miR-491-5p, and PEG10 across PCa tissues and in vitro cell systems; subcellular localization analysis determined the cytoplasmic distribution of FOXD3-AS1; Cell proliferation, migratory and invasive capacities, as well as apoptosis, were assessed using CCK-8, transwell, and flow cytometric assays, respectively; dual-luciferase reporter assays verified the targeting relationships between molecules; statistical software was used for data analysis.

RESULTS: FOXD3-AS1 demonstrated substantial upregulation within prostate carcinoma tissues and cultured cells and was found to be predominantly localized within the cytoplasmic compartment. Functional experiments demonstrated that depleting FOXD3-AS1 strongly impeded cell multiplication, spread, and penetration, and enhanced apoptotic activity. Rescue assays demonstrated that co-intervention of miR-491-5p or its downstream target PEG10 could counteract the tumor-suppressive effects induced by FOXD3-AS1 silencing. Mechanistically, FOXD3-AS1 functions as a ceRNA, sequestering miR-491-5p to attenuate its repression of PEG10.

CONCLUSION: FOXD3-AS1 influences PCa cell behavior via the miR-491-5p/PEG10 axis.

PMID:41291383 | DOI:10.1007/s00432-025-06364-x

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