[SRSF2通过诱导FSP1的替代剪接和抑制铁变态反应促进胶质母细胞瘤细胞增殖】。]

Q3 Medicine
D Hua, X X Zhou, Q Wang, C Y Sun, C J Shi, W J Luo, Z D Jiang, S Z Yu
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引用次数: 0

摘要

目的研究富含丝氨酸/精氨酸的剪接因子 2 (SRSF2) 对胶质母细胞瘤细胞中铁细胞生成的影响及其可能机制。研究方法利用基因表达谱互动分析在线数据库2(GEPIA 2)和中国胶质瘤基因组图谱分析SRSF2在胶质母细胞瘤组织中的表达及其与患者预后的关系。为了验证在线数据库的研究结果,研究人员收集了天津医科大学总医院的胶质母细胞瘤和非肿瘤脑组织的病理切片,并使用免疫组化方法进行了分析。用 siRNA 沉默胶质母细胞瘤细胞中 SRSF2 基因的表达,并进行 Western 印迹分析。用 CCK8 检测细胞的增殖指数。使用 pcDNA3.1(+)-SRSF2 表达质粒进行挽救实验。利用胶质母细胞瘤细胞中铁离子和丙二醛的水平以及谷胱甘肽与氧化谷胱甘肽比例的变化来评估铁变态反应的活性。利用第三代测序技术,即牛津纳米孔技术(ONT)测序分析,监测了SRSF2诱导的基因表达和差异前核糖核酸替代剪接(PMAS)的变化。结果SRSF2在胶质母细胞瘤组织中的表达高于非肿瘤脑组织。免疫组化结果显示,胶质母细胞瘤组织中 SRSF2 的阳性率为 88.48%±4.60%,远高于非肿瘤脑组织中的 9.97%±4.57%。SRSF2 的表达与总生存率和无病生存率成反比(PPPP>0.05)。ONT测序结果显示,在胶质母细胞瘤细胞中沉默SRSF2可诱导铁突变抑制蛋白1(FSP1)的3'剪接位点发生显著变化。结论SRSF2可抑制胶质母细胞瘤细胞的铁变态反应并促进其增殖,这可能是通过调节FSP1 PMAS实现的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[SRSF2 promotes glioblastoma cell proliferation by inducing alternative splicing of FSP1 and inhibiting ferroptosis].

Objective: To investigate the effect of serine/arginine-rich splicing factor 2 (SRSF2) on ferroptosis and its possible mechanism in glioblastoma cells. Methods: The online database of gene expression profiling interactive analysis 2 (GEPIA 2) and Chinese Glioma Genome Atlas were used to analyze the expression of SRSF2 in glioblastoma tissue and its association with patients prognosis. To validate the findings of the online databases, the pathological sections of glioblastoma and non-tumor brain tissues from Tianjin Medical University General Hospital, Tianjin, China were collected and analyzed by using immunohistochemistry. Silencing SRSF2 gene expression in glioblastoma cells by siRNA was analyzed with Western blot. The proliferation index was detected by using CCK8 assay. The rescued experiment was conducted by using expression plasmid of pcDNA3.1(+)-SRSF2. The activity of ferroptosis was assessed by using the levels of iron ions and malondialdehyde in glioblastoma cells and the changes in the ratio of glutathione to oxidized glutathione. The changes of gene expression and differential pre-mRNA alternative splicing (PMAS) induced by SRSF2 were monitored by using the third-generation sequencing technology analysis, namely Oxford nanopore technologies (ONT) sequencing analysis. Results: SRSF2 expression was higher in glioblastoma tissues than non-tumor brain tissues. Immunohistochemistry also showed a positive rate of 88.48%±4.60% in glioblastoma tissue which was much higher than the 9.97%±4.57% in non-tumor brain tissue. The expression of SRSF2 was inversely correlated with overall and disease-free disease survivals (P<0.01). The proliferation index of glioblastoma cells was significantly reduced by silencing with SRSF2 siRNA (P<0.01) and could be reversed with transfection of exogenous SRSF2. The levels of intracellulariron ions and malondialdehyde increased (P<0.05), but the glutathione/oxidized glutathione ratio and the expression of key proteins in the glutathione pathway remained unchanged (P>0.05). ONT sequencing results showed that silencing SRSF2 in glioblastoma cells could induce a significant alternative 3' splice site change on ferroptosis suppressor protein 1 (FSP1). Conclusion: SRSF2 inhibits the ferroptosis in glioblastoma cells and promotes their proliferation, which may be achieved by regulating FSP1 PMAS.

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中华病理学杂志
中华病理学杂志 Medicine-Medicine (all)
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