title: Suppression of protein tyrosine phosphatase PTPN22 gene induces apoptosis in T-cell leukemia cell line (Jurkat) through the AKT and ERK pathways.
abstract: The aim of this study was to investigate the effect of specific PTPN22 small interfering RNAs (siRNAs) on the viability and induction of apoptosis in Jurkat cells and to evaluate apoptosis signaling pathways. In this study, Jurkat cells were transfected with specific PTPN22 siRNA. Relative PTPN22 mRNA expression was measured by Quantitative Real-time PCR. Western blotting was performed to determine the protein levels of PTPN22, AKT, P-AKT, ERK, and P-ERK. The cytotoxic effects of PTPN22 siRNA were determined using the MTT assay. Apoptosis was quantified using TUNEL assay and flow cytometry. Results showed that in Jurkat cells after transfection with PTPN22 siRNA, the expression of PTPN22 in both mRNA and protein levels was effectively reduced. Moreover, siRNA transfection induced apoptosis on the viability of T-cell acute leukemia cells. More importantly, PTPN22 positively regulated the anti-apoptotic AKT kinase, which provides a powerful survival signal to T-ALL cells as well as the suppression of PTPN22 down regulated ERK activity. Our results suggest that the PTPN22 specific siRNA effectively decreases the viability of T-cell acute leukemia cells, induces apoptosis in this cell line, and therefore could be considered as a potent adjuvant in T-ALL therapy.
authors.affiliation: Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Baghbani
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Behzad
authors.initials: B
authors.lastname: Baradaran
authors.affiliation: Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Pak
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Mohammadnejad
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Daryoush
authors.initials: D
authors.lastname: Shanehbandi
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Behzad
authors.initials: B
authors.lastname: Mansoori
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Khaze
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Noushin
authors.initials: N
authors.lastname: Montazami
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Mohammadi
authors.affiliation: Cancer Research Center and Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran; Immune and Gene Therapy Lab, Cancer Centre Karolinska, Karolinska University Hospital, Stockholm, Sweden. Electronic address: Parviz.kokhaei@ki.se.
authors.forename: Parviz
authors.initials: P
authors.lastname: Kokhaei
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D055785:Gene Knockdown Techniques / Q000379:methods; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22
keywords: AKT; Apoptosis; ERK; Jurkat; Protein tyrosine phosphatase non-receptor type 22; T-cell leukemia; siRNA