The PCAT3/PCAT9-miR-203-SNAI2 axis functions as a key mediator for prostate tumor growth and progression
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Fangfang Tao1,*, Xinxin Tian2,3,* and Zhiqian Zhang3,4
1Department of Immunology and Microbiology, Basic Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, People's Republic of China
2Department of Biochemistry and Biophysics, Texas A and M University and Texas AgriLife Research, College Station, TX 77843-2128, USA
3Tianjin International Joint Academy of Biomedicine (TJAB), Tianjin 300457, People's Republic of China
4State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, People's Republic of China
*These authors contributed equally to this work
Zhiqian Zhang, email: email@example.com
Keywords: prostate cancer; LncRNAs; PCAT3; PCAT9; miR-203-SNAI2 axis
Received: September 26, 2017 Accepted: December 05, 2017 Published: January 12, 2018
Long non-coding RNAs (lncRNAs) have been reported to be of great importance in the formation and progression of a wide range of human carcinomas including prostate cancer (PCa). Among them, PCAT3 and PCAT9 have been identified as two prostate tissue-specific lncRNAs and are up-regulated in PCa. However, their roles in the biological characteristics of PCa have not been fully elucidated. In the present study, our data revealed that knockdown of PCAT3 and PCAT9 suppressed cellular proliferation, invasion, migration, angiogenesis and stemness in androgen-dependent LNCaP and 22Rv1 cells. Strikingly, bioinformatics analysis predicted that both PCAT3 and PCAT9 transcripts had two conserved binding sties for miR-203. Meanwhile, dual luciferase report assays revealed that miR-203 could suppress the luciferase activities of reporter plasmids carrying the binding site of miR-203 on the mRNA of PCAT3 or PCAT9. Quantitative RT-PCR (qRT-PCR) and RNA fluorescence in situ hybridization (RNA-FISH) showed that miR-203 mimic reduced the expression of PCAT3 and PCAT9 both in LNCaP and 22Rv1 cells. We also noted that both PCAT3 and PCAT9 inhibited miR-203 expression and alleviated repression on the expression of SNAI2, a critical regulator of epithelial-mesenchymal transition directly targeted by miR-203. Functionally, silence of miR-203 or ectopic expression of SNAI2 attenuated the inhibitory effect of PCAT3 and PCAT9 knockdown on cell proliferation and migration in vitro, and xenograft growth in vivo. Taken together, our data suggested that the PCAT3/PCAT9-miR-203-SNAI2 axis may serve as a promising diagnostic and therapeutic target for PCa.
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