Synthetic Tet-inducible small hairpin RNAs targeting hTERT or Bcl-2 inhibit malignant phenotypes of bladder cancer T24 and 5637 cells

Junhao Lin, Yuchen Liu, Yonghao Zhan, Chengle Zhuang, Li Liu, Xing Fu, Wen Xu, Jianfa Li, Mingwei Chen, Zhiming Cai, Weiren Huang

Small hairpin RNA (shRNA) can inhibit the malignant phenotypes of tumor cell through ribonucleic acid interference (RNAi). However, it is hardly to be regulated and it may induce few phenotypic changes. Here, we build a type of tetracycline (Tet)-inducible vectors which can achieve regulatable expression of shRNA in a time-dependent manner by using synthetic biology approach. In order to prove the effectiveness of this device, we chose hTERT and Bcl-2 as target genes and test the utility of the device on 5637 and T24 cell lines. The experiments show that the Tet-inducible small hairpin RNA can effectively suppress their target genes and generate anti-cancer effects on both 5637 and T24 cell lines. The device we build not only can inhibit proliferation but also can induce apoptosis and suppress migration of the bladder cancer cell lines 5637 and T24. The Tet-inducible small hairpin RNAs may provide a novel strategy for the treatment of human bladder cancer in the future.