The Impact of SRSF1-Mediated Alternative Splicing of RBBP6 on the Proliferation of Multiple Myeloma Cells
10.19746/j.cnki.issn1009-2137.2024.06.016
- VernacularTitle:SRSF1调控RBBP6发生可变剪接事件对多发性骨髓瘤细胞增殖的影响
- Author:
Wei-Min ZHANG
1
;
Sha SONG
;
Wen-Zhuo ZHUANG
;
Bing-Zong LI
Author Information
1. 苏州大学附属第二医院血液科,江苏苏州 215006
- Keywords:
multiple myeloma;
alternative splicing;
splicing factor SRSF1;
RBBP6
- From:
Journal of Experimental Hematology
2024;32(6):1738-1743
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of different isoforms of RBBP6 on the proliferation of multiple myeloma (MM) cells after alternative splicing mediated by splicing factor SRSF1. Methods:RT-PCR was used to detect the expression levels of RBBP6 mRNA splicing isoforms regulated by SRSF1. The GEO database was used to analyze the changes of RBBP6 isoform 1 in the progression of plasma cell disease,and survival analysis was used to evaluate the value of this gene in the prognosis of MM patients. In vitro loss-of-function and gain-of-function experiments were conducted by transfecting control siRNA,RBBP6 isoform 1 siRNA,empty vector (EV),OE-RBBP6 isoform 3 into MM.1S cells,then the expression levels of RBBP6 isoform 1 and RBBP6 isoform 3 were detected by real-time PCR and Western blot. CCK-8 assay was performed to detect the cell proliferation ability. Results:Knockdown of SRSF1 increased the expression of RBBP6 isoform 3 and decreased the expression of RBBP6 isoform 1. RBBP6 isoform 1 was closely related to the progression of plasma cell disease,and the high expression of RBBP6 isoform 1 was associated with poor prognosis in patients with MM. Downregulation of RBBP6 isoform 1 expression and overexpression of RBBP6 isoform 3 both reduced the proliferation ability of MM cells. And after downregulating the expression of RBBP6 isoform 1,the level of p53 protein in MM cells was significantly increased (P<0.05). Conclusion:In MM,splicing factor SRSF1 can cause alternative splicing abnormalities in RBBP6. The RBBP6 isoform 1 promotes MM cell proliferation,while the RBBP6 isoform 3 inhibits MM cell proliferation,and the mechanism may be related to regulating the p53 pathway.
