Zhang Yongxiao, Li Yinghua, Shi Rui
Department of Hematopathology, Hengshui People's Hospital, Hengshui 053000, China. *Corresponding author, E-mail:
Department of Hematopathology, Hengshui People's Hospital, Hengshui 053000, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2025 Mar;41(3):221-227.
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 therapeutic target for myelodysplastic syndromes.
目的 探讨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增殖和凋亡的调控作用及其潜在机制。方法 通过转染外源性SOCS1过表达质粒使SKM-1细胞中SOCS1过表达。分别采用CCK-8法和流式细胞术分析细胞活力、细胞周期及凋亡情况。采用蛋白质免疫印迹法评估与Janus激酶2/信号转导及转录激活因子（JAK2/STAT）信号通路相关蛋白的表达。此外，建立MDS的NOD/SCID小鼠模型，记录小鼠体重和生存时间，评估SOCS1基因对SKM-1细胞体内生长的影响。结果 转染SOCS1过表达质粒显著提高了MDS细胞系SKM-1中SOCS1的mRNA和蛋白表达水平。SOCS1过表达显著降低了细胞活力，抑制了SKM-1细胞的增殖并促进其凋亡，同时也降低了磷酸化JAK2（p-JAK2）、磷酸化STAT3（p-STAT3）和p-STAT5蛋白的表达。此外，体内实验结果显示，SOCS1过表达组小鼠的体重和生存时间显著优于MDS模型组，外周血中CD45 SKM-1细胞数量显著低于MDS模型组，表明SOCS1过表达可抑制小鼠体内SKM-1细胞的活性。蛋白质免疫印迹结果证实，SOCS1过表达组小鼠骨髓中SOCS1的蛋白表达水平显著高于MDS模型组，而p-JAK2、p-STAT3和p-STAT5的蛋白表达水平显著低于MDS模型组。结论 SOCS1通过负向调节JAK2/STAT信号通路抑制MDS细胞系SKM-1的增殖并促进其凋亡，使其成为骨髓增生异常综合征的潜在治疗靶点。
