-
Tytuł:
-
Neutrophil elastase-mediated proteolysis of the tumor suppressor p200 CUX1 promotes cell proliferation and inhibits cell differentiation in APL.
-
Autorzy:
-
Yu L; Clinical Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
Zhong L; Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Xiong L; Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
Dan W; Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
Li J; Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Ye J; Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Wan P; Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
Luo X; Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
Chu X; Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
Liu C; Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
He C; Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
Mu F; Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Liu B; Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China; Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China. Electronic address: .
-
Źródło:
-
Life sciences [Life Sci] 2020 Feb 01; Vol. 242, pp. 117229. Date of Electronic Publication: 2019 Dec 27.
-
Typ publikacji:
-
Journal Article
-
Język:
-
English
-
Imprint Name(s):
-
Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
-
MeSH Terms:
-
Homeodomain Proteins/*metabolism
Leukemia, Promyelocytic, Acute/*enzymology
Leukocyte Elastase/*metabolism
Repressor Proteins/*metabolism
Transcription Factors/*metabolism
Adolescent ; Adult ; Blotting, Western ; Cell Differentiation/physiology ; Cell Line, Tumor ; Cell Proliferation/physiology ; Female ; Flow Cytometry ; Fluorescent Antibody Technique, Indirect ; HL-60 Cells ; Homeodomain Proteins/physiology ; Humans ; Immunoprecipitation ; Leukemia, Promyelocytic, Acute/metabolism ; Leukocyte Elastase/physiology ; Male ; Proteolysis ; Real-Time Polymerase Chain Reaction ; Repressor Proteins/physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors/physiology ; U937 Cells
-
Contributed Indexing:
-
Keywords: Acute promyelocytic leukemia; Cut-like homeobox 1; Differentiation; Neutrophil elastase; Proliferation; Proteolysis
-
Substance Nomenclature:
-
0 (CUX1 protein, human)
0 (Homeodomain Proteins)
0 (Repressor Proteins)
0 (Transcription Factors)
EC 3.4.21.37 (Leukocyte Elastase)
-
Entry Date(s):
-
Date Created: 20191231 Date Completed: 20200128 Latest Revision: 20230907
-
Update Code:
-
20240104
-
DOI:
-
10.1016/j.lfs.2019.117229
-
PMID:
-
31887298
-
Aims: Neutrophil elastase (NE) is a critical proteolytic enzyme that is involved in cancer. We previously reported high NE expression in peripheral blood neutrophils from acute promyelocytic leukemia (APL) patients. The present study aimed to elucidate the specific role and mechanisms of NE in APL development.
Materials and Methods: NE expression was detected in APL bone marrow samples and analyzed in the BloodSpot database. CCK-8 assay and flow cytometry were used to assess cell proliferation and cell cycle distribution, respectively. The expression levels of proliferation and differentiation markers were measured by Western blotting and quantitative real-time PCR. The co-expression and interaction of NE and p200 cut-like homeobox 1 (CUX1) were evaluated by indirect immunofluorescence, co-immunoprecipitation, and in situ proximity ligation assay.
Key Findings: NE was highly expressed in APL bone marrow and blood neutrophils. NE overexpression promoted the proliferation and inhibited the differentiation of NB4 cells, whereas NE downregulation achieved the opposite results in U937 cells. Mechanistically, NE interacted with and effectively hydrolyzed the tumor suppressor p200 CUX1. Rescue experiments revealed that p200 CUX1 upregulation reversed the functional influence of NE on APL cells.
Significance: NE-mediated proteolysis of the tumor suppressor p200 CUX1 promotes APL progression. NE/p200 CUX1 axis is a novel and promising therapeutic target for APL treatment.
(Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
