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Circ-ABCC4 contributes to prostate cancer progression and radioresistance by mediating miR-1253/SOX4 cascade

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Circular RNAs (circRNAs) exert pivotal functions in many malignancies. However, the roles of circ-ABCC4 in prostate cancer (PCa) radioresistance and progression remain largely unclear. Cell viability, proliferation, apoptosis, invasion, and… Click to show full abstract

Circular RNAs (circRNAs) exert pivotal functions in many malignancies. However, the roles of circ-ABCC4 in prostate cancer (PCa) radioresistance and progression remain largely unclear. Cell viability, proliferation, apoptosis, invasion, and radioresistance were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, 5-ethynyl-2’-deoxyuridine, flow cytometry, transwell invasion, and colony formation assays. Tumor xenograft experiment was conducted to assess circ-ABCC4 role in xenograft growth in vivo. Dual-luciferase reporter assay was implemented to test the target relation of microRNA-1253 (miR-1253) and circ-ABCC4 or SRY-box transcription factor 4 (SOX4). Circ-ABCC4 enrichment was prominently raised in PCa tissue specimens and cells. Circ-ABCC4 depletion blocked PCa cell viability, proliferation, invasion, and radioresistance and triggered apoptosis. Circ-ABCC4 silencing aggravated irradiation-induced inhibitory effect on xenografts growth. miR-1253 was a downstream molecule of circ-ABCC4, and circ-ABCC4 depletion-mediated anti-cancer impacts in PCa cells were partly counteracted by decreasing miR-1253 abundance. miR-1253 targeted SOX4 mRNA, and miR-1253 blocked PCa cell malignant phenotypes partly by targeting SOX4. Circ-ABCC4 could enhance SOX4 abundance by absorbing miR-1253. Circ-ABCC4 exerted a pro-tumor activity by facilitating PCa cell viability, proliferation, invasion, and radioresistance and suppressing apoptosis.

Keywords: circ abcc4; radioresistance; mir 1253

Journal Title: Anti-Cancer Drugs
Year Published: 2022

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