shRNA targeting long non-coding RNA CCAT2 controlled by tetracycline-inducible system inhibits progression of bladder cancer cells

被引:61
作者
Li, Jianfa [1 ,2 ]
Zhuang, Chengle [1 ,2 ]
Liu, Yuchen [1 ]
Chen, Mingwei [1 ,3 ]
Zhou, Qing [1 ]
Chen, Zhicong [1 ,2 ]
He, Anbang [1 ,3 ]
Zhao, Guoping [4 ]
Guo, Yinglu [5 ]
Wu, Hanwei [1 ]
Cai, Zhiming [1 ,2 ,3 ,5 ]
Huang, Weiren [1 ,2 ,3 ,5 ]
机构
[1] Shenzhen Univ, Shenzhen Peoples Hosp 2, Affiliated Hosp 1, Key Lab Med Reprogramming Technol, Shenzhen, Peoples R China
[2] Shantou Univ, Coll Med, Shantou, Peoples R China
[3] Anhui Med Univ, Hefei, Peoples R China
[4] Chinese Natl Human Genome Ctr Shanghai, Shanghai MOST Key Lab Hlth & Dis Genom, Shanghai, Peoples R China
[5] Peking Univ, Natl Urol Canc Ctr, Dept Urol, Hosp 1,Inst Urol, Beijing 100871, Peoples R China
基金
美国国家科学基金会; 中国国家自然科学基金;
关键词
CCAT2; bladder cancer; lncRNAs; tetracycline-inducible; double shRNAs; SYNTHETIC BIOLOGY; GENE-EXPRESSION; POOR-PROGNOSIS; PROMOTES; EVOLUTION; GROWTH;
D O I
10.18632/oncotarget.8259
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Recent reports show that long non-coding RNAs (lncRNAs) are emerging as significant functional regulators in the development of tumors, including bladder cancer. Here, we found that CCAT2 was upregulated in bladder cancer tissues and cell lines. Through the statistical analyses, we also found that the high expression level of CCAT2 was positively correlated with histological grade and TNM stage of bladder cancer. Further experimental results revealed that knockdown of CCAT2 could decrease cell proliferation and migration as well as induce apoptosis in bladder cancer cells. Besides, using the post-transcriptional device of synthetic biology, we create the tetracycline-inducible double small hairpin RNAs (shRNAs) vector to control the expression level of CCAT2 which was induced by doxycycline in a dosage-dependent manner. In summary, our data indicated that CCAT2 may be an oncogene and a therapeutic target in bladder cancer. The expression of CCAT2 can be quantitatively controlled by the synthetic "tetracycline-on" switch system in bladder cancer in response to different concentrations of doxycycline to inhibit the development of bladder cancer cells.
引用
收藏
页码:28989 / 28997
页数:9
相关论文
共 27 条
[1]   Long Noncoding RNAs: Cellular Address Codes in Development and Disease [J].
Batista, Pedro J. ;
Chang, Howard Y. .
CELL, 2013, 152 (06) :1298-1307
[2]   Long noncoding RNA CCAT2 promotes breast tumor growth by regulating the Wnt signaling pathway [J].
Cai, Yi ;
He, Jing ;
Zhang, Dong .
ONCOTARGETS AND THERAPY, 2015, 8 :2657-2664
[3]   A long noncoding RNA AB073614 promotes tumorigenesis and predicts poor prognosis in ovarian cancer [J].
Cheng, Zhongping ;
Guo, Jing ;
Chen, Li ;
Luo, Ning ;
Yang, Weihong ;
Qu, Xiaoyan .
ONCOTARGET, 2015, 6 (28) :25381-25389
[4]   RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts [J].
Geisler, Sarah ;
Coller, Jeff .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2013, 14 (11) :699-712
[5]   Regulatable gene expression systems for gene therapy applications: Progress and future challenges [J].
Goverdhana, S ;
Puntel, M ;
Xiong, W ;
Zirger, JM ;
Barcia, C ;
Curtin, JF ;
Soffer, EB ;
Mondkar, S ;
King, GD ;
Hu, J ;
Sciascia, SA ;
Candolfi, M ;
Greengold, DS ;
Lowenstein, PR ;
Castro, MG .
MOLECULAR THERAPY, 2005, 12 (02) :189-211
[6]   Synthetic Biology-Toward Therapeutic Solutions [J].
Haellman, Viktor ;
Fussenegger, Martin .
JOURNAL OF MOLECULAR BIOLOGY, 2016, 428 (05) :945-962
[7]   Bladder Cancer in 2010 How Far Have We Come? [J].
Jacobs, Bruce L. ;
Lee, Cheryl T. ;
Montie, James E. .
CA-A CANCER JOURNAL FOR CLINICIANS, 2010, 60 (04) :244-272
[8]   Chromatin regulation at the frontier of synthetic biology [J].
Keung, Albert J. ;
Joung, J. Keith ;
Khalil, Ahmad S. ;
Collins, James J. .
NATURE REVIEWS GENETICS, 2015, 16 (03) :159-171
[9]  
Kis Z, 2015, J R SOC INTERFACE, V6, P12
[10]  
Li LJ, 2014, INT J CLIN EXP PATHO, V7, P7196