Background: Prostate cancer, an epithelial malignancy occurring in the prostate, is the most common malignant tumor of the male genitourinary system and has a low survival rate in advanced prostate cancer after metastasis. It is urgent to explore novel therapeutic targets and strategies for treating prostate cancer. Circular RNA (circRNA) and ferroptosis both play critical roles in prostate cancer progression. However, the regulatory effect of circRNA on ferroptosis remains unclear.Methods: Here, circRNA expression profiles in prostate cancer were explored by bioinformatics analysis and human prostate cancer tissue microarray. Stable circRNA-knockdown or overexpressed prostate cancer cell lines were constructed by lentivirus. AGO2-RNA immunoprecipitation (AGO2-RIP) was utilized to identify circRNA-microRNA (miRNA) interaction.Results: Results of this study indicate that circATP2C1 is highly expressed in prostate cancer. In addition, circATP2C1 promotes prostate cancer cell proliferation, migration, and invasion by suppressing ferroptosis in vitro. Moreover, circATP2C1 facilitates the tumorigenicity of prostate cancer by inhibiting ferroptosis in vivo.Conclusions: Mechanistically, circATP2C1 hinders ferroptosis by increasing solute carrier family 7 member 11 (SLC7A11) expression via sponging miR-654-3p. In summary, our findings highlight the oncogenic role of circATP2C1 in prostate cancer and provide novel targets and strategies for treating prostate cancer.
背景：前列腺癌是发生在前列腺的上皮性恶性肿瘤，是男性泌尿生殖系统最常见的恶性肿瘤，晚期前列腺癌转移后生存率较低。探索治疗前列腺癌的新靶点和策略迫在眉睫。环状RNA（circRNA）和铁死亡在前列腺癌进展中均发挥关键作用。然而，circRNA对铁死亡的调控作用尚不明确。 方法：本研究通过生物信息学分析和人前列腺癌组织芯片探索前列腺癌中circRNA的表达谱。利用慢病毒构建稳定的circRNA敲低或过表达的前列腺癌细胞系。采用AGO2-RNA免疫沉淀（AGO2-RIP）技术鉴定circRNA与微小RNA（miRNA）的相互作用。 结果：本研究结果表明，circATP2C1在前列腺癌中高表达。此外，circATP2C1在体外通过抑制铁死亡促进前列腺癌细胞增殖、迁移和侵袭。而且，circATP2C1在体内通过抑制铁死亡增强前列腺癌的致瘤性。 结论：从机制上讲，circATP2C1通过吸附miR-654-3p增加溶质载体家族7成员11（SLC7A11）的表达，从而阻碍铁死亡。总之，我们的研究结果揭示了circATP2C1在前列腺癌中的致癌作用，并为治疗前列腺癌提供了新的靶点和策略。
肿瘤(癌症)患者之家