CircSCAF8 promotes growth and metastasis of prostate cancer through the circSCAF8-miR-140-3p/miR-335-LIF pathway.
CircSCAF8 promotes growth and metastasis of prostate cancer through the circSCAF8-miR-140-3p/miR-335-LIF pathway.
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DOI：
10.1038/s41419-022-04913-7
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发表时间：
2022-06-02
影响因子：
9
通讯作者：
Li, Liao-Yuan
中科院分区：
文献类型：
--
作者：
He, Tao;Tao, Wen;Zhang, Lei-Lei;Wang, Bang-Yu;Li, Ke;Lu, Hui-Min;Tang, Guo-Jun;He, Ya-Di;Li, Liao-Yuan
环状RNA（circRNAs）与癌症进展的关联日益受到关注。然而，circRNAs在前列腺癌（PCa）中的详细生物学功能仍不明确。我们先前通过高通量circRNA测序，鉴定出18种尿液细胞外囊泡circRNAs，与良性前列腺增生患者相比，这些circRNAs在前列腺癌患者中表达上调。对30例前列腺癌患者肿瘤组织与配对尿液细胞外囊泡中这18种circRNAs的表达水平进行Spearman相关性分析，结果显示circSCAF8的R²值最高（R² = 0.635，P < 0.001）。采用Cox比例风险回归模型评估circSCAF8对无进展生存期的影响。通过体外和体内功能实验，探究circSCAF8对前列腺癌表型的作用。我们发现，在前列腺癌细胞中敲低circSCAF8可抑制细胞增殖、迁移和侵袭能力，而circSCAF8过表达则产生相反效果。体内实验也观察到类似结果。在85例接受根治性前列腺切除术的患者队列中，前列腺癌组织中circSCAF8的表达是无进展生存期的有力预测指标（风险比HR = 2.14，P = 0.022）。从机制上讲，circSCAF8可通过与miR - 140 - 3p和miR - 335结合，调节白血病抑制因子（LIF）的表达，激活LIF - STAT3信号通路，从而促进前列腺癌的生长和转移。综上所述，我们的研究结果表明，circSCAF8通过circSCAF8 - miR - 140 - 3p/miR - 335 - LIF信号通路促进前列腺癌进展。
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 R2 (R2 = 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.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
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影响因子：
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作者：
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作者：
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作者：
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作者：
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通讯作者：
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