Abstract
Therapeutic gene silencing is a promising approach for treatment of cancer. Despite substantial efforts, however, only few such therapeutic methods have been clinically tested. The heterogeneity in gene expression profiles among malignant tissues and the dynamic control of gene expression in individual tumors makes identifying universal and effective targets a challenge. Further development of gene silencing therapy requires new approaches to comprehend and manage gene expression in cancer cells. In this study, we proposed and evaluated experimentally a new approach to design multi-gene silencing therapy. Using a simplified model of gene expression control, we show that genes commonly regulated by the same microRNA represent optimal combinations of targets for small hairpin RNA/small interfering RNA-based gene silencing. The proposed method of target gene selection and co-silencing can be explored as an algorithm for personalized cancer gene therapy.
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Rodon J, Perez J, Kurzrock R . Combining targeted therapies: practical issues to consider at the bench and bedside. Oncologist 2010; 15: 37–50.
Li C, Zhang X, Cheng L, Dai L, Xu F, Zhang J et al. RNA interference targeting human FAK and EGFR suppresses human non-small-cell lung cancer xenograft growth in nude mice. Cancer Gene Ther 2013; 20: 101–108.
Shahzad MM, Lu C, Lee JW, Stone RL, Mitra R, Mangala LS et al. Dual targeting of EphA2 and FAK in ovarian carcinoma. Cancer Biol Ther 2009; 8: 1027–1034.
Punt CJ, Tol J . More is less -- combining targeted therapies in metastatic colorectal cancer. Nat Rev Clin Oncol 2009; 6: 731–733.
Bhardwaj N, Yan KK, Gerstein MB . Analysis of diverse regulatory networks in a hierarchical context shows consistent tendencies for collaboration in the middle levels. Proc Natl Acad Sci USA 2010; 107: 6841–6846.
Malek A, Bakhidze E, Noske A, Sers C, Aigner A, Schäfer R et al. HMGA2 gene is a promising target for ovarian cancer silencing therapy. Int J Cancer 2008; 123: 348–356.
Malek A, Schafer R, Tchernitsa O . Target genes suitable for silencing approaches and protein product interference in ovarian epithelial cancer. Cancer Treat Rev 2010; 36: 8–15.
Zhang S, Li Q, Liu J, Zhou XJ . A novel computational framework for simultaneous integration of multiple types of genomic data to identify microRNA-gene regulatory modules. Bioinformatics 2011; 27: i401–i409.
Zhdanov VP . Kinetic models of gene expression including non-coding RNAs. Physics Reports 2011; 500: 1–42.
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Malek, A., Gyorffy, B., Catapano, C. et al. Selection of optimal combinations of target genes for therapeutic multi-gene silencing based on miRNA co-regulation. Cancer Gene Ther 20, 326–329 (2013). https://doi.org/10.1038/cgt.2013.20
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DOI: https://doi.org/10.1038/cgt.2013.20
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