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.
周坚, 潘晓冉, 李小娟. miRNA-34a通过调控SOX4/RAS/MAPK信号通路对中枢神经系统淋巴瘤进展的影响[J]. 河北医学, 2023, 29(2): 189-194.
ZHOU Jian, PAN Xiaoran, LI Xiaojuan. Effect of miRNA-34a on the Progression of Central Nervous System Lymphoma by Regulating SOX4/RAS/MAPK Signaling Pathway. HeBei Med, 2023, 29(2): 189-194.
[1] Holdhoff M,Mrugala MM,Grommes C,et al.Challenges in the treatment of newly diagnosed and recurrent primary central nervous system lymphoma[J].Natl Compr Canc Netw,2020,18(11):1571-1578. [2] Calimeri T,Steffanoni S,Gagliardi F,et al.How we treat primary central nervous system lymphoma[J].ESMO Open,2021,6(4):100213. [3] Tabaei S,Tabaee SS.Implications for MicroRNA involvement in the prognosis and treatment of atherosclerosis[J].Mol Cell Biochem,2021,476(3):1327-1336. [4] Shan C,Chen X,Cai H,et al.The emerging roles of autophagy-related microRNAs in cancer[J].Int Biol Sci,2021,17(1):134-150. [5] Li Z,Chen H.miR-34a inhibits proliferation,migration and invasion of paediatric neuroblastoma cells via targeting HNF4α[J].Artif Cells Nanomed Biotechnol,2019,47(1):3072-3078. [6] Moreno CS.SOX4:The unappreciated oncogene[J].Semin Cancer Biol,2020,67(Pt 1):57-64. [7] Petri BJ,Klinge CM.Regulation of breast cancer metastasis signaling by miRNAs[J].Cancer Metastasis Rev,2020,39(3):837-886. [8] Xu XP,Peng XQ,Yin XM,et al.miR-34a-5p suppresses the invasion and metastasis of liver cancer by targeting the transcription factor YY1 to mediate MYCT1 upregulation[J].Acta Histochem,2020,122(6):151576. [9] Li X,Zhao S,Fu Y,et al.miR-34a-5p functions as a tumor suppressor in head and neck squamous cell cancer progression by targeting Flotillin-2[J].Int Biol Sci,2021,17(15):4327-4339. [10] Ramezani-Rad P,Geng H,Hurtz C,et al.SOX4 enables oncogenic survival signals in acute lymphoblastic leukemia[J].Blood,2013,121(1):148-155. [11] Takashima Y,Sasaki Y,Hayano A,et al.Target amplicon exome-sequencing identifies promising diagnosis and prognostic markers involved in RTK-RAS and PI3K-AKT signaling as central oncopathways in primary central nervous system lymphoma[J].Oncotarget,2018,9(44):27471-27486.
2023, Vol. 29 
冀公网安备13080202000677号