Synthetic regulatory RNAs selectively suppress the progression of bladder cancer

Journal of Experimental & Clinical Cancer Research

Changshui Zhuang¹  Xinbo Huang¹  Zhiming Cai¹  Xiaomin Luo¹  Yaoting Gui¹  Chengle Zhuang¹  Xiaowei Zhang² 

[1] Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen-Peking University-the Hong Kong University of Science and Technology Medical Center;The Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center;

关键词: Bladder cancer;    Human telomerase reverse transcriptase;    Artificial miRNA;    GAL4;   

DOI  :  10.1186/s13046-017-0626-x

来源: DOAJ

【 摘 要 】

Abstract The traditional treatment for cancer is lack of specificity and efficacy. Modular synthetic regulatory RNAs, such as inhibitive RNA (iRNA) and active RNA (aRNA), may overcome these limitations. Here, we synthesize a new iRNA to bind the upstream activating sequence (UAS) of a minimal promoter that drives expression of artificial miRNAs (amiRNAs) targeting MYC, which represses the binding interaction between UAS and GAL4 fusion protein (GAL4-VP64) in GAL4/UAS system. The aRNA driven by a tumor-specific mutant human telomerase reverse transcriptase (hTERT) promoter is created to interact with iRNA to expose UAS again in bladder cancer. Without the aRNA, mRNA and protein levels of MYC, cell growth, cell apoptosis and cell migration were no significance in two bladder cancer cell lines, T24 and 5637, and human foreskin fibroblast (HFF) cells. The aRNA significantly inhibited the expression of MYC in mRNA and protein levels, as well as the proliferation and migration of the cancer cells, but not in HFF cells. These results indicated that regulatory RNAs selectively controlled the expression of amiRNAs and ultimately suppress the progression of bladder cancer cells without affecting normal cells. Synthetic regulatory RNAs might be a selective therapeutic approach for bladder cancer.

【 授权许可】

Unknown