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

Zhongguo Shi Yan Xue Ye Xue Za Zhi

Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.

Published: December 2024

Objective: To investigate the effect of different isoforms of on the proliferation of multiple myeloma (MM) cells after alternative splicing mediated by splicing factor .

Methods: RT-PCR was used to detect the expression levels of mRNA splicing isoforms regulated by . The GEO database was used to analyze the changes of 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. loss-of-function and gain-of-function experiments were conducted by transfecting control siRNA, isoform 1 siRNA, empty vector (EV), OE- isoform 3 into MM.1S cells, then the expression levels of isoform 1 and 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 increased the expression of isoform 3 and decreased the expression of isoform 1. isoform 1 was closely related to the progression of plasma cell disease, and the high expression of isoform 1 was associated with poor prognosis in patients with MM. Downregulation of isoform 1 expression and overexpression of isoform 3 both reduced the proliferation ability of MM cells. And after downregulating the expression of isoform 1, the level of p53 protein in MM cells was significantly increased ( < 0.05).

Conclusion: In MM, splicing factor can cause alternative splicing abnormalities in . The isoform 1 promotes MM cell proliferation, while the isoform 3 inhibits MM cell proliferation, and the mechanism may be related to regulating the p53 pathway.

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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2024.06.016DOI Listing

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