The protein signal transducer and activator of transcription 5 (STAT5) of the JAK/STAT pathway is constitutively activated because of its phosphorylation by tyrosine kinase activity of fusion protein BCR-ABL in chronic myelogenous leukemia (CML) cells. This study investigated the potential therapeutic effect of STAT5 decoy oligodeoxynucleotides (ODN) using leukemia K562 cells as a model. Our results showed that transfection of 21-mer-long STAT5 decoy ODN into K562 cells effectively inhibited cell proliferation and induced cell apoptosis. Further, STAT5 decoy ODN downregulated STAT5 targets bcl-xL, cyclinD1, and c-myc at both mRNA and protein levels in a sequence-specific manner. Collectively, these data demonstrate the therapeutic effect of blocking the STAT5 signal pathway by cis-element decoy for cancer characterized by constitutive STAT5 activation. Thus, our study provides support for STAT5 as a potential target downstream of BCR-ABL for CML treatment and helps establish the concept of targeting STAT5 by decoy ODN as a novel therapy approach for imatinib-resistant CML.
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http://dx.doi.org/10.1089/dna.2010.1112 | DOI Listing |
Hum Immunol
November 2024
Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:
Chronic inflammatory skin conditions such as psoriasis and atopic dermatitis (AD) impose a significant burden on both the skin and the overall well-being of individuals, leading to a diminished quality of life. Despite the use of conventional treatments like topical steroids, there remains a need for more effective and safer therapeutic options to improve the lives of patients with severe skin conditions. Molecular therapy has emerged as a promising approach to address disorders such as atopic dermatitis, psoriasis, and contact hypersensitivity.
View Article and Find Full Text PDFMol Ther Nucleic Acids
March 2024
Department of Immuno-Oncology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
Decoy oligodeoxynucleotides (ODNs) allow targeting undruggable transcription factors, such as STAT3, but their limited potency and lack of delivery methods hampered translation. To overcome these challenges, we conjugated a STAT3-specific decoy to thalidomide, a ligand to cereblon in E3 ubiquitin ligase complex, to generate a proteolysis-targeting chimera (STAT3D). STAT3D downregulated STAT3 in target cells, but not STAT1 or STAT5.
View Article and Find Full Text PDFMol Ther Nucleic Acids
December 2023
Department of Pathology, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea.
Atopic dermatitis (AD) is a common inflammatory skin disease caused by an immune disorder. Mast cells are known to be activated and granulated to maintain an allergic reaction, including rhinitis, asthma, and AD. Although hypoxia-inducible factor-1 alpha (HIF-1α) and signal transducer and activator of transcription 5 (STAT5) play crucial roles in mast cell survival and granulation, their effects need to be clarified in allergic disorders.
View Article and Find Full Text PDFJ Neurochem
November 2016
Area of Neuroscience, SISSA, Trieste, Italy.
Erythropoietin receptor (EpoR) regulates erythrocytes differentiation in blood. In the brain, EpoR has been shown to protect several neuronal cell types from cell death, including the A9 dopaminergic neurons (DA) of the Substantia Nigra (SN). These cells form the nigrostriatal pathway and are devoted to the control of postural reflexes and voluntary movements.
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