Transcription factor decoy against stem cells master regulators, Nanog and Oct-4: a possible approach for differentiation therapy
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Transcription factor decoys (TFDs) are exogenous oligonucleotides which can compete by cis-elements in promoters or enhancers for binding to TFs and downregulating gene expression in a specific manner. It is believed that tumor mass originates from cancer stem cells (CSCs) which the same with embryonic stem cells (ESCs) have the properties of both pluripotency and self-renewal (stemness). Many transcription factors such as Nanog, Oct-4, Sox2, Klf4, and Sall4 act as master regulators in the maintenance of stemness in both cell types. Differentiation therapy is based on this theory that by differentiation of CSCs, tumor mass can be eliminated with common cancer therapy methods. To our knowledge, the present study is the first report of a TFD approach against master regulator of stemness, Nanog, Oct-4, and Klf4, for downregulation purposes in P19 embryonic carcinoma stem cell. Different simple and complex decoys against Nanog, OCT-4, Sox2, and Klf4 were designed and used for this purpose. The results showed that the applied decoys especially Nanog-specific decoy decreased the expression of downstream genes.
KeywordsTranscription factor decoy Stemness Cancer Stem Cells P19 cells Nanog
This project has been funded by Tarbiat Modares University and Iran National Science Foundation under contract no. 88000962. The authors also thank Stem Cell Technology Research Center which supported some parts of the experiments and appreciate Nadia Chamani for the assistance in preparing figures.
Conflicts of interest
Authors disclose any commercial associations that might create a conflict of interest in connection with submitted manuscripts.
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