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Cancer Lett. 2019 Oct 5. pii: S0304-3835(19)30497-5. doi: 10.1016/j.canlet.2019.10.006. [Epub ahead of print]

Reduction of circular RNA Foxo3 promotes prostate cancer progression and chemoresistance to docetaxel.

Author information

1
Department of Urology, Huadong Hospital, Fudan University, 221 West Yan'an Road, Shanghai, 200040, China.
2
Department of Thyroid Surgery, China-Japan Union Hospital, Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun, 130033, China.
3
Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, Guangzhou, China.
4
Department of Urology, Huadong Hospital, Fudan University, 221 West Yan'an Road, Shanghai, 200040, China. Electronic address: doctor_x@126.com.

Abstract

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.

KEYWORDS:

chemoresistance; circFoxo3; epithelialmesenchymal transition (EMT); prostate cancer

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