Biomaterial Database

[The Effect of SP1 on the Progression of T-cell Acute Lymphoblastic Leukemia]. 2023

Shi Tang, and Hao-Biao Wang, and Wei Guo, and Lin Zou, and Shan Liu

Center for Clinical Molecular Medicine, Children's Hospital Affiliated to Chongqing Medical University,Chongqing 400014, China.National Clinical Research Center for Child Health and Disorders,Chongqing 400014, China.Ministry of Education Key Laboratory of Child Development and Disorders,Chongqing 400014, China.Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.

OBJECTIVE To study the transcriptional regulation of SP1 on the scaffold protein ARRB1 and its influence on the progression of T-cell acute lymphoblastic leukemia (T-ALL). METHODS pGL3-ARRB1-luc, pCDNA3.1-SP1 and other transcription factor plasmids that might be combined were constructed, and the binding of transcription factors to the promoter of ARRB1 was identified by dual luciferase reporter gene assay. Stable cell lines with over-expressed SP1 (JK-SP1) was constructed by lentiviral transfection, and the expression correlation of SP1 with ARRB1 was demonstrated by RT-PCR and Western blot. Further, the apoptosis, cell cycle and reactive oxygen species (ROS) were detected by flow cytometry. The effect of SP1 on propagation of leukemic cells was observed on NCG leukemic mice. RESULTS The expression of fluorescein were enhanced by co-transfection with pCDNA3.1-SP1 and pGL3-ARRB1-luc plasmids in HEK293T cell line (P<0.001), meanwhile, compared with the control group, the expression of ARRB1 mRNA and protein were increased in JK-SP1 cells (both P<0.01). Further in vitro experiments showed that, compared with the control group, the apoptosis rate was higher (x=22.78%) , the cell cycle was mostly blocked in G1 phase (63.00%), and the content of reactive oxygen species increased in JK-SP1 cells. And in vivo experiments showed that the mice injected with JK-SP1 cells through tail vein had a favorable overall survival time (average 33.8 days), less infiltration in liver and spleen tissue. CONCLUSIONS Transcription factor SP1 promotes the transcription and expression of ARRB1 by binding the the promoter of ARRB1 directly, thus delays the progress of T-ALL in vitro and in vivo. The study improves the pathogenesis of ARRB1 regulating the initiation and development of T-ALL, and provides theoretical basis for the development of new possible targeted drugs.

UI	MeSH Term	Description	Entries
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013601	T-Lymphocytes	Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.	T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D014157	Transcription Factors	Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.	Transcription Factor,Factor, Transcription,Factors, Transcription
D016329	Sp1 Transcription Factor	Promoter-specific RNA polymerase II transcription factor that binds to the GC box, one of the upstream promoter elements, in mammalian cells. The binding of Sp1 is necessary for the initiation of transcription in the promoters of a variety of cellular and viral GENES.	Transcription Factor, Sp1,Specificity Protein 1 Transcription Factor
D017382	Reactive Oxygen Species	Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.	Active Oxygen Species,Oxygen Radical,Oxygen Radicals,Pro-Oxidant,Reactive Oxygen Intermediates,Active Oxygen,Oxygen Species, Reactive,Pro-Oxidants,Oxygen, Active,Pro Oxidant,Pro Oxidants,Radical, Oxygen
D045744	Cell Line, Tumor	A cell line derived from cultured tumor cells.	Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D054218	Precursor T-Cell Lymphoblastic Leukemia-Lymphoma	A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.	Leukemia, Lymphoblastic, Acute, T-Cell,Leukemia, Lymphocytic, Acute, T-Cell,Leukemia, T-Cell, Acute,Lymphoblastic Leukemia, Acute, T-Cell,Lymphocytic Leukemia, T-Cell, Acute,T-ALL,T-Cell Leukemia, Acute,T-Lymphocytic Leukemia, Acute,Leukemia, Lymphoblastic, Acute, T Cell,Leukemia, Lymphocytic, Acute T Cell,Lymphoblastic Leukemia, Acute, T Cell,Lymphocytic Leukemia, T Cell, Acute,Precursor T-Cell Lymphoblastic Leukemia,Precursor T-Cell Lymphoblastic Lymphoma,T-Cell Acute Lymphocytic Leukemia,Acute T-Cell Leukemia,Acute T-Cell Leukemias,Acute T-Lymphocytic Leukemia,Acute T-Lymphocytic Leukemias,Leukemia, Acute T-Cell,Leukemia, Acute T-Lymphocytic,Leukemias, Acute T-Cell,Leukemias, Acute T-Lymphocytic,Precursor T Cell Lymphoblastic Leukemia,Precursor T Cell Lymphoblastic Leukemia Lymphoma,Precursor T Cell Lymphoblastic Lymphoma,T Cell Leukemia, Acute,T Lymphocytic Leukemia, Acute,T-Cell Leukemias, Acute,T-Lymphocytic Leukemias, Acute
D057809	HEK293 Cells	A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.	293T Cells,HEK 293 Cell Line,HEK 293 Cells,Human Embryonic Kidney Cell Line 293,Human Kidney Cell Line 293,293 Cell, HEK,293 Cells, HEK,293T Cell,Cell, 293T,Cell, HEK 293,Cell, HEK293,Cells, 293T,Cells, HEK 293,Cells, HEK293,HEK 293 Cell,HEK293 Cell