Development of a computational promoter with highly efficient expression in tumors
Abstract 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 ca...
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doaj-cd64f3d16cac4607bf660cb5bd6c57a62020-11-25T02:15:32ZengBMCBMC Cancer1471-24072018-04-0118111510.1186/s12885-018-4421-7Development of a computational promoter with highly efficient expression in tumorsShu-Yi Ho0Bo-Hau Chang1Chen-Han Chung2Yu-Ling Lin3Cheng-Hsun Chuang4Pei-Jung Hsieh5Wei-Chih Huang6Nu-Man Tsai7Sheng-Chieh Huang8Yen-Ku Liu9Yu-Chih Lo10Kuang-Wen Liao11Department of Biological Science and Technology, National Chiao Tung UniversityDepartment of Biological Science and Technology, National Chiao Tung UniversityInstitute of Molecular Medicine and Bioengineering, National Chiao Tung UniversityDepartment of Biological Science and Technology, National Chiao Tung UniversityInstitute of Molecular Medicine and Bioengineering, National Chiao Tung UniversityDepartment of Biological Science and Technology, National Chiao Tung UniversityInstitute of Bioinformatics and Systems Biology, National Chiao Tung UniversitySchool of Medical and Laboratory Biotechnology, Chung Shan Medical UniversityDepartment of Surgery, National Yang Ming UniversityInstitute of Molecular Medicine and Bioengineering, National Chiao Tung UniversityDepartment of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung UniversityDepartment of Biological Science and Technology, National Chiao Tung UniversityAbstract 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.http://link.springer.com/article/10.1186/s12885-018-4421-7Gene therapyTranscription factorHIF-1αNF-κB and CREB |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shu-Yi Ho Bo-Hau Chang Chen-Han Chung Yu-Ling Lin Cheng-Hsun Chuang Pei-Jung Hsieh Wei-Chih Huang Nu-Man Tsai Sheng-Chieh Huang Yen-Ku Liu Yu-Chih Lo Kuang-Wen Liao |
spellingShingle |
Shu-Yi Ho Bo-Hau Chang Chen-Han Chung Yu-Ling Lin Cheng-Hsun Chuang Pei-Jung Hsieh Wei-Chih Huang Nu-Man Tsai Sheng-Chieh Huang Yen-Ku Liu Yu-Chih Lo Kuang-Wen Liao Development of a computational promoter with highly efficient expression in tumors BMC Cancer Gene therapy Transcription factor HIF-1α NF-κB and CREB |
author_facet |
Shu-Yi Ho Bo-Hau Chang Chen-Han Chung Yu-Ling Lin Cheng-Hsun Chuang Pei-Jung Hsieh Wei-Chih Huang Nu-Man Tsai Sheng-Chieh Huang Yen-Ku Liu Yu-Chih Lo Kuang-Wen Liao |
author_sort |
Shu-Yi Ho |
title |
Development of a computational promoter with highly efficient expression in tumors |
title_short |
Development of a computational promoter with highly efficient expression in tumors |
title_full |
Development of a computational promoter with highly efficient expression in tumors |
title_fullStr |
Development of a computational promoter with highly efficient expression in tumors |
title_full_unstemmed |
Development of a computational promoter with highly efficient expression in tumors |
title_sort |
development of a computational promoter with highly efficient expression in tumors |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2018-04-01 |
description |
Abstract 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. |
topic |
Gene therapy Transcription factor HIF-1α NF-κB and CREB |
url |
http://link.springer.com/article/10.1186/s12885-018-4421-7 |
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