SOCS1基因对骨髓增生异常综合征细胞的生长抑制作用及其潜在机制  

The inhibition effect of SOCS1 gene on the growth of human myelodysplastic syndrome cells and its potential mechanisms

作　　者：张永晓 李英华 石锐 ZHANG Yongxiao;LI Yinghua;SHI Rui(Department of Hematopathology,Hengshui People’s Hospital,Hengshui 053000,China)

机构地区：[1]衡水市人民医院血液内科,河北衡水053000

出　　处：《细胞与分子免疫学杂志》2025年第3期221-227,共7页Chinese Journal of Cellular and Molecular Immunology

基　　金：衡水市科技计划项目(2023014037Z)。

摘　　要：目的 检测细胞因子信号转导抑制因子1(SOCS1)对骨髓增生异常综合征(MDS)细胞SKM-1细胞增殖、凋亡的调控作用及其潜在的作用机制。方法 通过转染外源性SOCS1过表达质粒促进SKM-1细胞内SOCS1的表达,CCK-8法检测细胞活力,流式细胞术检测细胞周期和细胞凋亡,Western blot法检测Janus激酶2/信号转导子与转录激活子(JAK2/STAT)信号通路相关蛋白的表达。通过构建NOD/SCID小鼠MDS模型,记录小鼠体质量及生存时间,评估SOCS1基因对体内SKM-1细胞生长的影响。结果 在MDS细胞株SKM-1细胞中转染SOCS1过表达质粒可显著提高SOCS1 mRNA和蛋白表达水平。过表达SOCS1可显著降低SKM-1细胞活力,抑制细胞增殖,促进细胞凋亡;同时降低细胞内磷酸化的JAK2(p-JAK2)、磷酸化的STAT3(p-STAT3)和p-STAT5蛋白的表达。动物实验结果显示SOCS1过表达组小鼠体质量及生存时间显著优于MDS模型组,外周血中CD45^(+) SKM-1细胞数量显著低于MDS模型组,说明过表达SOCS1可抑制小鼠体内SKM-1细胞的活性;Western blot结果显示,SOCS1过表达组小鼠骨髓中SOCS1蛋白表达水平显著高于MDS模型组,而p-JAK2、 p-STAT3和p-STAT5蛋白的表达水平则显著低于MDS模型组。结论 SOCS1可通过负调控JAK2/STAT信号通路抑制MDS细胞系SKM-1细胞的增殖,并促进其凋亡,可作为治疗骨髓增生异常综合征的潜在靶点。Objective To investigate the regulatory effect of suppressor of cytokine signaling 1(SOCS1)on the proliferation and apoptosis of myelodysplastic syndrome(MDS)cells SKM-1 and its potential mechanisms.Methods SOCS1 was overexpressed in SKM-1 cells by transfection with exogenous SOCS1-overexpressing plasmid.Cell viability,cell cycle and apoptosis were analyzed with CCK-8 and flow cytometry assays,respectively.Western blot was used to evaluate the expression of proteins related to the Janus kinase 2/signal transducer and activator of transcription(JAK2/STAT)signaling pathway.Additionally,a NOD/SCID mouse model of MDS was established to record mouse body weight and survival time,assessing the impact of the SOCS1 gene on the growth of SKM-1 cells in vivo.Results Transfection of the SOCS1-overexpressing plasmid significantly increased the mRNA and protein expression levels of SOCS1 in the MDS cell line SKM-1.Overexpression of SOCS1 remarkably reduced cell viability,inhibited cell proliferation,and promoted apoptosis of SKM-1 cells,which also decreased the expression of phosphorylated-JAK2(p-JAK2),phosphorylated-STAT3(p-STAT3),and p-STAT5 proteins.Furthermore,in vivo experiment results showed that the body weight and survival time of mice in the SOCS1 overexpression group were significantly better than those in the MDS model group,and the number of CD45^(+)SKM-1 cells in the peripheral blood was significantly lower than that in the MDS model group,indicating that SOCS1 overexpression could inhibit the activity of SKM-1 cells in mice.Western blot results verified the protein expression level of SOCS1 in the bone marrow of mice in the SOCS1 overexpression group was significantly higher than that in the MDS model group,while the protein expression levels of p-JAK2, p-STAT3, and p-STAT5 were significantly lower than those in the MDS model group. Conclusion SOCS1 inhibits the proliferation of MDS cell line SKM-1 and promotes its apoptosis by negatively regulating the JAK2/STAT signaling pathway, making it a potential therapeu

关 键 词：细胞因子信号转导抑制因子1(SOCS1) 骨髓增生异常综合征(MDS) 细胞增殖 细胞凋亡 JAK2/STAT信号通路 

分 类 号：R392[医药卫生—免疫学] R551.3[医药卫生—基础医学]