Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Department of Breast Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Cell Death Dis. 2022 Jun 2;13(6):517. doi: 10.1038/s41419-022-04913-7.
Circular RNAs (circRNAs) have been increasingly linked to cancer progression. However, the detailed biological functions of circRNAs in prostate cancer (PCa) remain unclear. Using high-throughput circRNA sequencing, we previously identified 18 urine extracellular vesicle circRNAs that were increased in patients with PCa compared with those with benign prostatic hyperplasia. Spearman correlation analysis of the expression levels of the 18 circRNAs between the tumor tissue and matched urine extracellular vesicles in 30 PCa patients showed that circSCAF8 had the highest R (R = 0.635, P < 0.001). The Cox proportional hazards regression model was used to estimate the effect of circSCAF8 on progression-free survival. The in vitro and in vivo functional experiments were implemented to investigate the effects of circSCAF8 on the phenotype of PCa. We found that the knockdown of circSCAF8 in PCa cells suppressed the proliferation, migration, and invasion ability, while overexpression of circSCAF8 had the opposite effects. Similar results were observed in vivo. In a cohort of 85 patients who had undergone radical prostatectomy, circSCAF8 expression in PCa tissues was a powerful predictor of progression-free survival (HR = 2.14, P = 0.022). Mechanistically, circSCAF8 can function by binding to both miR-140-3p and miR-335 to regulate LIF expression and activate the LIF-STAT3 pathway that leads to the growth and metastasis of PCa. Collectively, our findings demonstrate that circSCAF8 contributes to PCa progression through the circSCAF8-miR-140-3p/miR-335-LIF pathway.
环状 RNA（circRNAs）与癌症进展的关系越来越密切。然而，circRNAs 在前列腺癌（PCa）中的详细生物学功能仍不清楚。我们之前使用高通量 circRNA 测序，发现与良性前列腺增生患者相比，18 种尿液外泌体 circRNAs 在 PCa 患者中升高。在 30 名 PCa 患者的肿瘤组织和匹配的尿液外泌体中，对 18 种 circRNAs 的表达水平进行 Spearman 相关分析显示，circSCAF8 的 R 值最高（R=0.635，P<0.001）。Cox 比例风险回归模型用于估计 circSCAF8 对无进展生存期的影响。进行了体外和体内功能实验，以研究 circSCAF8 对 PCa 表型的影响。我们发现，在 PCa 细胞中敲低 circSCAF8 抑制了增殖、迁移和侵袭能力，而过表达 circSCAF8 则产生相反的效果。在体内也观察到了类似的结果。在 85 名接受根治性前列腺切除术的患者队列中，PCa 组织中 circSCAF8 的表达是无进展生存期的有力预测因子（HR=2.14，P=0.022）。从机制上讲，circSCAF8 可以通过与 miR-140-3p 和 miR-335 结合来发挥作用，调节 LIF 的表达并激活 LIF-STAT3 通路，导致 PCa 的生长和转移。总之，我们的研究结果表明，circSCAF8 通过 circSCAF8-miR-140-3p/miR-335-LIF 通路促进 PCa 的进展。
