Effect of U2AF1 Mutation to Inflammatory Cytokine Expression in SKM-1 Cells through FOXO3a-Bim Signaling Pathway.
10.19746/j.cnki.issn.1009-2137.2021.06.028
- Author:
Yu-Qian ZHU
1
;
Ling-Yun WU
2
Author Information
1. Department of Hematology, The Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, China.
2. Department of Hematology, The Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, China,E-mail: lincy2032@163.com.
- Publication Type:Journal Article
- MeSH:
Cytokines;
Forkhead Box Protein O3/metabolism*;
Humans;
Mutation;
Signal Transduction;
Splicing Factor U2AF
- From:
Journal of Experimental Hematology
2021;29(6):1858-1863
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of U2AF1 gene mutation to inflammatory cytokine in SKM-1 cell of human myelodysplastic syndromes (MDS), and whether the above effects were mediated by FOXO3a-Bim signaling pathway.
METHODS:Wide-type U2AF1 and mutant U2AF1 (the serine residue 34 was replaced by phenylalanine, and named as S34F) recombinant expression plasmids were constructed. Lentiviruses were packaged and transfected into SKM-1 cells. The expression of FOXO3a was up-regulated by lentiviruses, and its transfection rate was investigated. The cell proliferation was detected by CCK-8 method. Flow cytometry was used to detect the apoptosis and cycle of the cells. The expression pro-inflammatory cytokine IL-1β, IL-6, TNF-α and anti-inflammatory cytokine IL-4 were detected by qRT-PCR. FOXO3a, Bim, Bcl-2 and Bax protein expression levels were detected by Western blot.
RESULTS:Compared with the control group, the cell apoptosis rate, pro-inflammatory cytokine IL-1β and TNF-α transcription levels were significantly increased in the S34F group (P<0.05); cell cycle was blocked at the G
CONCLUSION:U2AF1 S34F mutation can regulate inflammatory phenotype in SKM-1 cells, which may be mediated through FOXO3a-Bim signaling pathway.
