β-arrestin 1 Promotes Senescence of Acute Lymphoblastic Leukemia Jurkat Cells.
10.19746/j.cnki.issn.1009-2137.2019.03.022
- Author:
Wei GUO
1
;
Shan LIU
1
;
Hai-Yan LIU
1
;
Yan-Hua CHEN
1
;
Hang ZHANG
1
;
Wen-Qiong LYU
1
;
Lin ZOU
2
Author Information
1. Center for Clinical Molecular Medicine, Children's Hospital, Chongqing Medical University; Ministry of Education Key Laboratory of Child Development and Disorders; Key Laboratory of Pediatrics in Chongqing; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, China.
2. Center for Clinical Molecular Medicine, Children's Hospital, Chongqing Medical University; Ministry of Education Key Laboratory of Child Development and Disorders; Key Laboratory of Pediatrics in Chongqing; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, China,E-mail: zoulin74@hotmail.com.
- Publication Type:Journal Article
- MeSH:
Cellular Senescence;
Humans;
Jurkat Cells;
Precursor Cell Lymphoblastic Leukemia-Lymphoma;
genetics;
Prognosis;
beta-Arrestin 1;
genetics
- From:
Journal of Experimental Hematology
2019;27(3):777-784
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of β-arrestin1 gene on senescence of T-ALL cells and its possible mechanism.
METHODS:The bone marrow specimens of T-ALL patients and controls were collected, the expression of β-arrestin1 and β-arrestin1 in the T-ALL patients was detected by RT-PCR and Western blot, respectively, and the relation of β-arrestin1 expression with the clinical pathologic characteristics and the prognosis of T-ALL patients was analyzed statistically. The stable Jurkat cell line with knocked down or overexpressed β-arrestin1 was constructed, the CCK method was used to detect the Jurkat cell number, the β-gal staining was used to analyze the effect of β-arrestin1 on senescence of Jurkat cells, the cross analysis of RNA-Seg data and KEGG data was performed for screening the possible signaling pathway, and Western blot was performed for varifying the key sites of signaling pathway.
RESULTS:The β-arrestin1 expression in specimens of T-ALL patients decreased (P＜0.01), moreover the β-arrestin1 expression negatively related with peripheral blood cell number (r=-0.601), the blasts in peripheral blood (r=-0.516) and extramedullary infiltration (r=-0.359), while positively related with the response to chemotherapy (r=0.393). The detection of stable Jurkat cell line with knocked-down and overexpressed β-arrestin1 found that the β-arrestin 1 could decrease the Jurkat cell number and accelarate the senescence of Jurkat cells (P＜0.05). The cross analysis of RNA-Seg data and KEGG data showed that the senescence of T-ALL cells may be regulated via RAS-P16-PRb-E2F1 by β-arrestin 1. Western bolt confirmed that β-arrestin1 promoted the expression of Ras and p16, and decreased the expression of pRB and E2F1 (P＜0.05).
CONCLUSIONS:β-arrestin1 accelerates the senescence of Jurkat cells via Ras-p16-pRb-E2F1, and delays the progression in T-ALL, which may provide a new hypothesis for the pathogenesis of T-ALL.
