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| Effect of miRNA-34a on the Progression of Central Nervous System Lymphoma by Regulating SOX4/RAS/MAPK Signaling Pathway |
| ZHOU Jian, PAN Xiaoran, LI Xiaojuan |
| Hunan Provincial Brain Hospital / The Second People's Hospital of Hunan, Hunan Changsha 410000, China |
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Abstract Objective: To investigate the role of microRNA-34a (miR-34a) in primary central nervous system lymphoma (PCNSL) and its underlying molecular mechanisms. Methods: The expression of miR-34a in PCNSL tissues was detected by real-time quantitative PCR (RT-qPCR) experiments. Raji cell was cultured in vitro, and miR-34a mimic (miR-34a mimic), mimic control (NC mimic), miR-34a inhibitor (miR-34a inhibitor), inhibitor control (NC inhibitor), miR-34a mimic+Blank plasmid (Vector) and miR-34a mimic+SOX4 overexpression plasmid (pcDNA-SOX4) were transfected into cells respectively. The RT-qPCR assay was used to detect the expression of miR-34a in cells. Cell proliferation ability was detected by CCK-8 assay and clone formation assay. The apoptosis rate was detected by flow cytometry. Western blot was used to detect the expression of SOX4 protein and RAS/MAPK pathway proteins Ras, p-Raf-1, and p-MEK in cells. Bioinformatics software and dual luciferase reporter assay were used to predict and verify the targeting relationship between miR-34a and SOX4, respectively. Results: The expression of miR-34a in PCNSL tissues was significantly decreased (P<0.05). Compared with the NC mimic group, the expression of miR-34a in the miR-34a mimic group was increased, the cell proliferation ability was significantly decreased, the apoptosis rate was significantly increased, the protein expressions of Ras, p-Raf-1, and p-MEK were significantly decreased (P<0.05). Compared with the NC inhibitor group, the expression of miR-34a in the miR-34a inhibitor group was decreased, the cell proliferation ability was significantly increased, the apoptosis rate was significantly decreased, the protein expressions of Ras, p-Raf-1, and p-MEK were significantly increased (P<0.05). Compared with the NC mimic group, the luciferase activity of cells co-transfected with miR-34a mimic and WT-SOX4 was significantly decreased (P<0.05), while there was no significant change in luciferase activity of cells co-transfected with miR-34a mimic and MUT-SOX4 (P>0.05). Compared with the miR-34a mimic+Vector group, the proliferation ability of Raji cells in the miR-34a mimic+pcDNA-SOX4 group was significantly increased, the apoptosis rate was significantly decreased, and the protein expressions of Ras, p-Raf-1, and p-MEK were significantly increased (P<0.05). Conclusion: miR-34a could inhibit PCNSL cell proliferation and promotes apoptosis by targeting SOX4 to regulate the RAS/MAPK signaling pathway.
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2023, Vol. 29 
