[The Impact of SRSF1 -Mediated Alternative Splicing of RBBP6 on the Proliferation of Multiple Myeloma Cells].

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.