The Effect of SP1 on the Progression of T-cell Acute Lymphoblastic Leukemia.
10.19746/j.cnki.issn.1009-2137.2023.01.009
- Author:
Shi TANG
1
;
Hao-Biao WANG
1
;
Wei GUO
1
;
Lin ZOU
2
;
Shan LIU
3
Author Information
1. 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.
2. Clinical Research Unit, Children's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200062, China.E-mail: zoulin74@126.com.
3. 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.E-mail: shanl@hospital.cqmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
ARRB1;
SP1;
T-cell acute lymphoblastic leukemia
- MeSH:
Humans;
Animals;
Mice;
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics*;
HEK293 Cells;
Reactive Oxygen Species;
Transcription Factors;
T-Lymphocytes;
Cell Line, Tumor;
Sp1 Transcription Factor/metabolism*
- From:
Journal of Experimental Hematology
2023;31(1):57-63
- CountryChina
- Language:Chinese
-
Abstract:
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.
CONCLUSION: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.
