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Development of a computational promoter with highly efficient expression in tumors.
Ho, Shu-Yi; Chang, Bo-Hau; Chung, Chen-Han; Lin, Yu-Ling; Chuang, Cheng-Hsun; Hsieh, Pei-Jung; Huang, Wei-Chih; Tsai, Nu-Man; Huang, Sheng-Chieh; Liu, Yen-Ku; Lo, Yu-Chih; Liao, Kuang-Wen.
Afiliación
  • Ho SY; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, Republic of China.
  • Chang BH; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, Republic of China.
  • Chung CH; Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, 30050, Taiwan, Republic of China.
  • Lin YL; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, Republic of China.
  • Chuang CH; Center for Bioinformatics Research, National Chiao Tung University, Hsinchu, Taiwan, Republic of China.
  • Hsieh PJ; Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, 30050, Taiwan, Republic of China.
  • Huang WC; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, Republic of China.
  • Tsai NM; Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, 300, Taiwan, Republic of China.
  • Huang SC; School of Medical and Laboratory Biotechnology, Chung Shan Medical University, Taichung, Taiwan, Republic of China.
  • Liu YK; Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.
  • Lo YC; Department of Surgery, National Yang Ming University, Taipei, Taiwan, Republic of China.
  • Liao KW; Division of Colon and Rectal surgery, Department of surgery, Taipei Veteran General Hospital, Taipei, Taiwan, Republic of China.
BMC Cancer ; 18(1): 480, 2018 04 27.
Article en En | MEDLINE | ID: mdl-29703163
BACKGROUND: Gene therapy is a potent method to increase the therapeutic efficacy against cancer. However, a gene that is specifically expressed in the tumor area has not been identified. In addition, nonspecific expression of therapeutic genes in normal tissues may cause side effects that can harm the patients' health. Certain promoters have been reported to drive therapeutic gene expression specifically in cancer cells; however, low expression levels of the target gene are a problem for providing good therapeutic efficacy. Therefore, a specific and highly expressive promoter is needed for cancer gene therapy. METHODS: Bioinformatics approaches were utilized to analyze transcription factors (TFs) from high-throughput data. Reverse transcription polymerase chain reaction, western blotting and cell transfection were applied for the measurement of mRNA, protein expression and activity. C57BL/6JNarl mice were injected with pD5-hrGFP to evaluate the expression of TFs. RESULTS: We analyzed bioinformatics data and identified three TFs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), cyclic AMP response element binding protein (CREB), and hypoxia-inducible factor-1α (HIF-1α), that are highly active in tumor cells. Here, we constructed a novel mini-promoter, D5, that is composed of the binding sites of the three TFs. The results show that the D5 promoter specifically drives therapeutic gene expression in tumor tissues and that the strength of the D5 promoter is directly proportional to tumor size. CONCLUSIONS: Our results show that bioinformatics may be a good tool for the selection of appropriate TFs and for the design of specific mini-promoters to improve cancer gene therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Regiones Promotoras Genéticas / Biología Computacional / Vectores Genéticos / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: BMC Cancer Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Regiones Promotoras Genéticas / Biología Computacional / Vectores Genéticos / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: BMC Cancer Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido