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Silent FOSL1 Enhances the Radiosensitivity of Glioma Stem Cells by Down-Regulating miR-27a-5p
Neurochemical Research ( IF 4.4 ) Pub Date : 2021-08-21 , DOI: 10.1007/s11064-021-03427-6
Rong Li 1 , Wuqiang Che 2 , Naizheng Liang 2 , Shu Deng 2 , Zhijie Song 2 , Lei Yang 2
Affiliation  

Since few reports have mentioned the role of FOSL1 in the radiotherapy sensitivity of glioma, this study would dig deep into this aspect. Cancer stem cells (CSCs) isolated by magnetic bead assay were identified by microscopy, qRT-PCR and western blot. The number of apoptotic cells was counted 72 h after X-ray irradiation to evaluate the sensitivity of cancer cells to radiotherapy. The effects of radiotherapy, FOSL1 and miR-27a-5p on basic cell functions were detected by functional experiments. The expressions of FOSL1, apoptosis-related genes and miR-27a-5p were detected by qRT-PCR and western blot as needed. The differential expression of FOSL1 and the effect of miR-27a-5p on survival rate were analyzed using GEPIA and UALCAN, respectively. FOSL1 was found highly expressed in glioma cells and patients. The appearance of spherical cells and high expressions of CSC-related markers indicated the successful isolation of CSC-like cells. The increment of X-ray dose enhanced the sensitivity of cancer cells to radiotherapy. Radiotherapy down-regulated cell viability and the expressions of FOSL1 and Bcl-2, but up-regulated cell apoptosis and the expressions of cleaved caspase-3 and Bax, which could be partially reversed by overexpressed FOSL1 or further enhanced by shFOSL1. MiR-27a-5p was highly expressed in in patients with glioma, which was associated with poor prognosis, while shFOSL1-inhibited miR-27a-5p expression enhanced the sensitivity of glioma stem cells to radiotherapy. In vivo experiments further verified the results obtained from in vitro experiments. Silent FOSL1 strengthened the radiosensitivity of glioma by down-regulating miR-27a-5p.



中文翻译:

沉默 FOSL1 通过下调 miR-27a-5p 增强胶质瘤干细胞的放射敏感性

由于很少有报道提及FOSL1在胶质瘤放疗敏感性中的作用,因此本研究将深入研究这方面。通过磁珠法分离的癌症干细胞 (CSC) 通过显微镜、qRT-PCR 和蛋白质印迹进行鉴定。X射线照射后72小时计数凋亡细胞数,以评价癌细胞对放疗的敏感性。通过功能实验检测放疗、FOSL1和miR-27a-5p对细胞基本功能的影响。根据需要通过qRT-PCR和western blot检测FOSL1、凋亡相关基因和miR-27a-5p的表达。分别使用GEPIA和UALCAN分析FOSL1的差异表达和miR-27a-5p对生存率的影响。FOSL1 在神经胶质瘤细胞和患者中高表达。球形细胞的出现和CSC相关标志物的高表达表明CSC样细胞的成功分离。X射线剂量的增加增强了癌细胞对放疗的敏感性。放疗下调细胞活力以及 FOSL1 和 Bcl-2 的表达,但上调细胞凋亡以及 cleaved caspase-3 和 Bax 的表达,这种情况可以通过过表达 FOSL1 部分逆转或通过 shFOSL1 进一步增强。miR-27a-5p在胶质瘤患者中高表达,与不良预后相关,而shFOSL1抑制miR-27a-5p表达可增强胶质瘤干细胞对放疗的敏感性。体内实验进一步验证了体外实验得到的结果。沉默的 FOSL1 通过下调 miR-27a-5p 增强神经胶质瘤的放射敏感性。

更新日期:2021-10-21
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