Literature DB >> 23358828

Suppression of STAT5A and STAT5B chronic myeloid leukemia cells via siRNA and antisense-oligonucleotide applications with the induction of apoptosis.

Burçin Tezcanlı Kaymaz1, Nur Selvi, Aysun Adan Gokbulut, Cağdaş Aktan, Cumhur Gündüz, Güray Saydam, Fahri Sahin, Vildan Bozok Cetintaş, Yusuf Baran, Buket Kosova.   

Abstract

Signal transducers and activators of transcription (STAT) proteins function in the JAK/STAT signaling pathway and are activated by phosphorylation. As a result of this signaling event, they affect many cellular processes including cell growth, proliferation, differentiation, and survival. Increases in the expressions of STAT5A and STAT5B play a remarkable role in the development of leukemia in which leukemic cells gain uncontrolled proliferation and angiogenesis ability. At the same time, these cells acquire ability to escape from apoptosis and host immune system. In this study, we aimed to suppress STAT-5A and -5B genes in K562 CML cells by siRNA transfection and antisense oligonucleotides (ODN) targeting and then to evaluate apoptosis rate. Finally, we compared the transfection efficiencies of these approaches. Quantitative RT-PCR and Western blot results indicated that STAT expressions were downregulated at both mRNA and protein levels following siRNA transfection. However, electroporation mediated ODN transfection could only provide limited suppression rates at mRNA and protein levels. Moreover, it was displayed that apoptosis were significantly induced in siRNA treated leukemic cells as compared to ODN treated cells. As a conclusion, siRNA applications were found to be more effective in terms of gene silencing when compared to ODN treatment based on the higher apoptosis and mRNA suppression rates. siRNA application could be a new and alternative curative method as a supporting therapy in CML patients.

Entities:  

Keywords:  Chronic myeloid leukemia; K562; STAT5; antisense oligonucleotides; apoptosis; siRNA knockdown

Year:  2013        PMID: 23358828      PMCID: PMC3555192     

Source DB:  PubMed          Journal:  Am J Blood Res        ISSN: 2160-1992


  25 in total

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2.  P210 and P190(BCR/ABL) induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members.

Authors:  R L Ilaria; R A Van Etten
Journal:  J Biol Chem       Date:  1996-12-06       Impact factor: 5.157

3.  Down-regulation of interleukin-3/granulocyte-macrophage colony-stimulating factor receptor beta-chain in BCR-ABL(+) human leukemic cells: association with loss of cytokine-mediated Stat-5 activation and protection from apoptosis after BCR-ABL inhibition.

Authors:  N J Donato; J Y Wu; L Zhang; H Kantarjian; M Talpaz
Journal:  Blood       Date:  2001-05-01       Impact factor: 22.113

4.  Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells.

Authors:  S M Elbashir; J Harborth; W Lendeckel; A Yalcin; K Weber; T Tuschl
Journal:  Nature       Date:  2001-05-24       Impact factor: 49.962

Review 5.  JAK/STAT signal transduction: regulators and implication in hematological malignancies.

Authors:  Lyne Valentino; Josiane Pierre
Journal:  Biochem Pharmacol       Date:  2006-01-19       Impact factor: 5.858

Review 6.  Divergent roles of STAT1 and STAT5 in malignancy as revealed by gene disruptions in mice.

Authors:  D E Levy; D G Gilliland
Journal:  Oncogene       Date:  2000-05-15       Impact factor: 9.867

Review 7.  siRNA and innate immunity.

Authors:  Marjorie Robbins; Adam Judge; Ian MacLachlan
Journal:  Oligonucleotides       Date:  2009-06

8.  The role of STAT5 proteins in the regulation of normal hematopoiesis in a cord blood model.

Authors:  Magdalena Baśkiewicz-Masiuk; Marek Masiuk; Ryszard Czajka; Bogusław Machaliński
Journal:  Cell Mol Biol Lett       Date:  2003       Impact factor: 5.787

9.  The influence of STAT5 antisense oligonucleotides on the proliferation and apoptosis of selected human leukaemic cell lines.

Authors:  M Baśkiewicz-Masiuk; M Masiuk; B Machaliński
Journal:  Cell Prolif       Date:  2003-10       Impact factor: 6.831

10.  Signal transducer and activator of transcription (STAT)5 activation by BCR/ABL is dependent on intact Src homology (SH)3 and SH2 domains of BCR/ABL and is required for leukemogenesis.

Authors:  M Nieborowska-Skorska; M A Wasik; A Slupianek; P Salomoni; T Kitamura; B Calabretta; T Skorski
Journal:  J Exp Med       Date:  1999-04-19       Impact factor: 14.307

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Review 2.  Pharmacogenetics and Pharmacogenomics of Targeted Therapeutics in Chronic Myeloid Leukemia.

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Journal:  Mol Diagn Ther       Date:  2017-12       Impact factor: 4.074

3.  Antiproliferative and proapoptotic effects of a pyrrole containing arylthioindole in human Jurkat leukemia cell line and multidrug-resistant Jurkat/A4 cells.

Authors:  Alex A Philchenkov; Michael P Zavelevich; Volodymyr P Tryndyak; Ludmila M Kuiava; Dmitry Yu Blokhin; Koh Miura; Romano Silvestri; Igor P Pogribny
Journal:  Cancer Biol Ther       Date:  2015       Impact factor: 4.742

Review 4.  STAT transcription factors in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention.

Authors:  K A Dorritie; J A McCubrey; D E Johnson
Journal:  Leukemia       Date:  2013-06-25       Impact factor: 11.528

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6.  Investigating the potential therapeutic role of targeting STAT3 for overcoming drug resistance by regulating energy metabolism in chronic myeloid leukemia cells.

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Review 7.  Co-operating STAT5 and AKT signaling pathways in chronic myeloid leukemia and mastocytosis: possible new targets of therapy.

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9.  Genome-wide identification of methylated CpG sites in nongenital cutaneous warts.

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Journal:  BMC Med Genomics       Date:  2020-07-08       Impact factor: 3.063

10.  Identification of consistent post-translational regulatory triplets related to oncogenic and tumour suppressive modulators in childhood acute lymphoblastic leukemia.

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  10 in total

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