Oncotarget

Research Papers:

Inhibition of long non-coding RNA UCA1 by CRISPR/Cas9 attenuated malignant phenotypes of bladder cancer

Shuai Zhen _, Ling Hua, Yun-Hui Liu, Xiao-Min Sun, Meng-Meng Jiang, Wei Chen, Le Zhao and Xu Li

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Oncotarget. 2017; 8:9634-9646. https://doi.org/10.18632/oncotarget.14176

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Abstract

Shuai Zhen1,2,*, Ling Hua3,*, Yun-Hui Liu4, Xiao-Min Sun5, Meng-Meng Jiang6, Wei Chen5, Le Zhao1,2, Xu Li1,2

1Center for Translational Medicine, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, P.R. China

2Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P.R. China

3Department of Veterinary Medicine, Rongchang Campus of Southwest University, Chongqing 402460, P.R. China

4Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China

5Center for Laboratory Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P.R. China

6State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi’an 710032, Shaanxi, China

*These authors have contributed equally to this work

Correspondence to:

Xu Li, email: lixu56@mail.xjtu.edu.cn

Le Zhao, email: zhaole2@mail.xjtu.edu.cn

Keywords: CRISPR/Cas9, long non-coding RNA, UCA1, bladder cancer

Received: January 16, 2016     Accepted: December 12, 2016     Published: December 25, 2016

ABSTRACT

CRISPR/Cas9 is a novel and effective genome editing technique, but its application is not widely expanded to manipulate long non-coding RNA (lncRNA) expression. The lncRNA urothelial carcinoma-associated 1 (UCA1) is upregulated in bladder cancer and promotes the progression of bladder cancer. Here, we design gRNAs specific to UCA1 and construct CRISPR/Cas9 systems targeting UCA1. Single CRISPR/Cas9-UCA1 can effectively inhibit UCA1 expression when transfected into 5637 and T24 bladder cancer cells, while the combined transfection of the two most effective CRISPR/Cas9-UCA1s can generate more satisfied inhibitory effect. CRISPR/Cas9-UCA1s attenuate UCA1 expression via targeted genome-specific DNA cleavage, resulting in the significant inhibition of cell proliferation, migration and invasion in vitro and in vivo. The mechanisms associated with the inhibitory effect of CRISPR/Cas9-UCA1 on malignant phenotypes of bladder cancer are attributed to the induction of cell cycle arrest at G1 phase, a substantial increase of apoptosis, and an enhanced activity of MMPs. Additionally, urinary UCA1 can be used as a non-invasive diagnostic marker for bladder cancer as revealed by a meta-analysis. Collectively, our data suggest that CRISPR/Cas9 technique can be used to down-modulate lncRNA expression, and urinary UCA1 may be used as a non-invasive marker for diagnosis of bladder cancer.


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