title: Transcription factor decoy against stem cells master regulators, Nanog and Oct-4: a possible approach for differentiation therapy.
abstract: 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.
authors.affiliation: Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran, Iran, a.hoseini.rad@gmail.com.
authors.forename: Seyed Mohammad Ali Hosseini
authors.initials: SM
authors.lastname: Rad
authors.forename: Taravat
authors.initials: T
authors.lastname: Bamdad
authors.forename: Majid
authors.initials: M
authors.lastname: Sadeghizadeh
authors.forename: Ehsan
authors.initials: E
authors.lastname: Arefian
authors.forename: Majid
authors.initials: M
authors.lastname: Lotfinia
authors.forename: Milad
authors.initials: M
authors.lastname: Ghanipour
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D053595:Embryonic Stem Cells; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000627:therapeutic use; D006801:Humans; D000090062:Kruppel-Like Factor 4; D000071317:Nanog Homeobox Protein; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics* / Q000627:therapeutic use; D009841:Oligonucleotides / Q000235:genetics / Q000627:therapeutic use*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics; D015398:Signal Transduction
chemical_list: D018398:Homeodomain Proteins; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D009841:Oligonucleotides; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors