Reduction of circular RNA Foxo3 promotes prostate cancer progression and chemoresistance to docetaxel
Reduction of circular RNA Foxo3 promotes prostate cancer progression and chemoresistance to docetaxel
复制标题
环状 RNA Foxo3 的减少促进前列腺癌进展和多西紫杉醇化疗耐药
DOI：
10.1016/j.canlet.2019.10.006
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发表时间：
2020-01-01
期刊：
影响因子：
9.7
通讯作者：
Xu, Jun
中科院分区：
文献类型：
--
作者：
Shen, Zhiyuan;Zhou, Le;Xu, Jun
据报道，环状RNA Foxo 3（circFoxo 3）的失调与乳腺癌和非小细胞肺癌的进展有关。然而，目前对circFoxo 3在前列腺癌中的作用知之甚少，本研究旨在调查。在22个低级别前列腺癌样品、24个高级别前列腺癌样品和18个正常前列腺组织中分析了CircFoxo 3表达，发现与低级别前列腺癌和正常前列腺组织相比，其量在高级别前列腺癌中显著降低。CircFoxo 3可抑制前列腺癌细胞的存活、迁移、侵袭和对多西他赛的耐药性，其机制与CircFoxo 3抑制Foxo 3和EMT有关。沉默circFoxo 3表达促进前列腺癌细胞存活、迁移、侵袭和对多西他赛的化学抗性，以及雄激素对前列腺癌生存力的积极作用。circfoxo 3的递送增强了前列腺荷瘤小鼠对多西他赛的化疗敏感性并延长了小鼠的寿命，而siRNA的减少促进了对多西他赛的化疗耐药性并缩短了荷瘤小鼠的寿命。靶向circFoxo 3/Foxo 3/EMT可能为探索前列腺癌的潜在预后和治疗方法提供一种适用的策略。
Dysregulation of circular RNA Foxo3 (circFoxo3) has been reported to be involved in breast cancer and non-small lung cancer progression. However, little is known about the role of circFoxo3 in prostate cancer, which the present study seeks to investigate. CircFoxo3 expression was analyzed in 22 low-grade prostate cancer samples, 24 high-graded prostate cancer samples, and 18 normal prostate tissues, finding that its quantity was significantly decreased in high-graded compared to low-grade prostate cancer and normal prostate tissues. CircFoxo3 inhibited prostate cancer cell survival, migration, invasion and chemoresistance to docetaxel, which was related to circFoxo3's repression of Foxo3 and EMT. Silencing circFoxo3 expression promoted prostate cancer cell survival, migration, invasion and chemoresistance to docetaxel, as well as the positive effects of androgen on prostate cancer viability. Delivery of circfoxo3 enhanced chemosensitivity to docetaxel of prostate tumor-bearing mice and prolonged the life span of mice, while reduction with siRNAs promoted chemoresistance to docetaxel and shorted the life span of the tumor-bearing mice. Targeting circFoxo3/Foxo3/EMT may provide an applicable strategy for exploring potential prognostic and therapeutic approaches for prostate cancer.