Rad Seyed Mohammad Ali Hosseini, Bamdad Taravat, Sadeghizadeh Majid, Arefian Ehsan, Lotfinia Majid, Ghanipour Milad
Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran, Iran,
Tumour Biol. 2015 Apr;36(4):2621-9. doi: 10.1007/s13277-014-2884-y. Epub 2014 Dec 3.
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.
转录因子诱饵（TFDs）是一种外源性寡核苷酸，它可以通过启动子或增强子中的顺式元件竞争与转录因子（TFs）结合，并以特定方式下调基因表达。据信，肿瘤块起源于癌症干细胞（CSCs），与胚胎干细胞（ESCs）一样，具有多能性和自我更新（干性）的特性。许多转录因子，如Nanog、Oct-4、Sox2、Klf4和Sall4，在维持这两种细胞类型的干性中起着主要调节作用。分化疗法基于这样一种理论，即通过癌症干细胞的分化，可以用常见的癌症治疗方法消除肿瘤块。据我们所知，本研究是首次报道一种针对干性主要调节因子Nanog、Oct-4和Klf4的TFD方法，用于下调P19胚胎癌干细胞中的这些因子。为此设计并使用了针对Nanog、OCT-4、Sox2和Klf4的不同简单和复杂诱饵。结果表明，所应用的诱饵，尤其是Nanog特异性诱饵，降低了下游基因的表达。
