title: Synthetic Tet-inducible artificial microRNAs targeting β-catenin or HIF-1α inhibit malignant phenotypes of bladder cancer cells T24 and 5637.
abstract: Ribonucleic acid interference (RNAi) based on microRNA (miRNA) may provide efficient and safe therapeutic opportunities. However, natural microRNAs can not easily be regulated and usually cause few phenotypic changes. Using the engineering principles of synthetic biology, we provided a novel and standard platform for the generation of tetracycline (Tet)-inducible vectors that express artificial microRNAs in a dosage-dependent manner. The vector generates a Pol II promoter-mediated artificial microRNA which was flanked by ribozyme sequences. In order to prove the utility of this platform, we chose β-catenin and HIF-1α as the functional targets and used the bladder cancer cell lines 5637 and T24 as the test models. We found that the Tet-inducible artificial microRNAs can effectively silence the target genes and their downstream genes, and induce anti-cancer effects in the two bladder cancer cell lines. These devices can inhibit proliferation, induce apoptosis, and suppress migration of the bladder cancer cell lines 5637 and T24. The Tet-inducible synthetic artificial microRNAs may represent a kind of novel therapeutic strategies for treating human bladder cancer.
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Shenzhen, China.|Shantou University Medical College, Shantou 515041, China.
authors.forename: Yonghao
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Shenzhen, China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Shenzhen, China.|Shantou University Medical College, Shantou 515041, China.
authors.forename: Junhao
authors.initials: J
authors.lastname: Lin
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Shenzhen, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Fu
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Shenzhen, China.|Shantou University Medical College, Shantou 515041, China.
authors.forename: Chengle
authors.initials: C
authors.lastname: Zhuang
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Shenzhen, China.|Shantou University Medical College, Shantou 515041, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Shenzhen, China.|School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Shenzhen, China.|Shantou University Medical College, Shantou 515041, China.
authors.forename: Jianfa
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Shenzhen, China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Centerat Shanghai, Shanghai 200000, Shanghai, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Shenzhen, China.
authors.forename: Weiren
authors.initials: W
authors.lastname: Huang
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Shenzhen, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D013752:Tetracycline / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035683:MicroRNAs; D051176:beta Catenin; D013752:Tetracycline