上调的环状 RNA hsa_circ_0067934 通过激活 PI3K-AKT 通路促进胶质母细胞瘤进展。
Up-regulated circular RNA hsa_circ_0067934 contributes to glioblastoma progression through activating PI3K-AKT pathway.
机构信息
Department of Neurosurgery, Linyi Center Hospital, Linyi, Shandong, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Apr;23(8):3447-3454. doi: 10.26355/eurrev_201904_17709.
OBJECTIVE
Circular RNAs (circRNAs) are involved in cancer progression and metastasis, although little is known about their role in glioblastoma (GBM). The aim of this study was to investigate the expression pattern and molecular mechanism of hsa_circ_0067934 in GBM.
PATIENTS AND METHODS
Hsa_circ_0067934 expression was detected in GBM tissues and cell lines by using RT-PCR. The prognostic value of the hsa_circ_0067934 expression in GBM patients was statistically analyzed. The effects of hsa_circ_0067934 expression on growth and apoptosis of GBM cells were analyzed by CCK-8, colony formation, and flow cytometry. Migration and invasion ability was evaluated by transwell and wound-healing assays. The protein expression of signaling pathways was determined by using Western blot.
RESULTS
The expression level of hsa_circ_0067934 was significantly increased in GBM tissues and cancer cells. Kaplan-Meier survival curves showed that patients with higher expression of hsa_circ_0067934 had a more favorable overall survival and disease-free survival. The functional investigations revealed that the knockdown of hsa_circ_0067934 suppressed GBM cell proliferation, metastasis and EMT, and promoted apoptosis. Moreover, the mechanistic analysis demonstrated that the down-regulation of hsa_circ_0067934 significantly suppressed the activation of the PI3K-AKT pathway.
CONCLUSIONS
Hsa_circ_0067934 is overexpressed and plays an oncogenic role in GBM by promoting cancer cell proliferation and metastasis via upregulation of PI3K-AKT pathway, which suggests that hsa_circ_0067934 is likely to serve as an efficient therapeutic approach in respect of GBM treatment.
目的
环状 RNA（circRNAs）参与癌症的进展和转移，尽管它们在脑胶质瘤（GBM）中的作用知之甚少。本研究旨在探讨 hsa_circ_0067934 在 GBM 中的表达模式和分子机制。
方法
采用 RT-PCR 检测 GBM 组织和细胞系中 hsa_circ_0067934 的表达。统计分析 hsa_circ_0067934 在 GBM 患者中的表达对预后的影响。通过 CCK-8、集落形成和流式细胞术分析 hsa_circ_0067934 表达对 GBM 细胞生长和凋亡的影响。通过 Transwell 和划痕愈合实验评估迁移和侵袭能力。通过 Western blot 测定信号通路的蛋白表达。
结果
hsa_circ_0067934 的表达水平在 GBM 组织和癌细胞中显著升高。Kaplan-Meier 生存曲线显示，hsa_circ_0067934 表达较高的患者总生存率和无病生存率更有利。功能研究表明，hsa_circ_0067934 的敲低抑制了 GBM 细胞的增殖、转移和 EMT，并促进了凋亡。此外，机制分析表明，hsa_circ_0067934 的下调显著抑制了 PI3K-AKT 通路的激活。
结论
hsa_circ_0067934 在 GBM 中过度表达，并通过上调 PI3K-AKT 通路促进癌细胞增殖和转移，发挥致癌作用，这表明 hsa_circ_0067934 可能成为治疗 GBM 的有效治疗方法。
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