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
,
2
,
3
,
4
;
Shan LIU
1
,
2
,
3
,
4
;
Hai-Yan LIU
1
,
2
,
3
,
4
;
Yan-Hua CHEN
1
,
2
,
3
,
4
;
Hang ZHANG
1
,
2
,
3
,
4
;
Wen-Qiong LYU
1
,
2
,
3
,
4
;
Lin ZOU
1
,
2
,
3
,
5
Author Information
1. Center for Clinical Molecular Medicine, Children's Hospital, Chongqing Medical University
2. Ministry of Education Key Laboratory of Child Development and Disorders
3. Key Laboratory of Pediatrics in Chongqing
4. Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, China.
5. 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.
