双重靶向 miR-21 和 CXCR4 敲低通过抑制 PI3K/AKT 和 Raf/MEK/ERK 通路抑制恶性胶质瘤进展。
Double-Targeted Knockdown of miR-21 and CXCR4 Inhibits Malignant Glioma Progression by Suppression of the PI3K/AKT and Raf/MEK/ERK Pathways.
机构信息
Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Neurosurgery of the Nanyang First People's Hospital, Nanyang, China.
出版信息
Biomed Res Int. 2020 Oct 15;2020:7930160. doi: 10.1155/2020/7930160. eCollection 2020.
Currently, miR-21 and CXCR4 are being extensively investigated as two key regulators in glioma malignancy. In this study, we investigated the combined effects of these two factors on glioma progression. Herein, the expression of miR-21 and CXCR4 was increased in tumor tissues and cell lines. Inhibition of miR-21, CXCR4, and miR-21 and CXCR4 together all reduced the migration, invasiveness, proliferation, and enhanced apoptosis in glioma cells, as well as reduced tumor volume and mass in xenograft model. The inhibition effect was strongest in double-targeted knockdown of miR-21 and CXCR4 group, whose downstream pathways involved in AKT axis and ERK axis activation. In conclusion, our findings reported that double-targeted knockdown of miR-21 and CXCR4 could more effectively inhibit the proliferation, migration, invasion, and growth of transplanted tumor and promote cell apoptosis, which were involved in the PI3K/AKT and Raf/MEK/ERK signaling pathways.
目前，miR-21 和 CXCR4 作为胶质瘤恶性的两个关键调节因子正在被广泛研究。在本研究中，我们研究了这两个因素对胶质瘤进展的联合影响。在此，miR-21 和 CXCR4 的表达在肿瘤组织和细胞系中增加。抑制 miR-21、CXCR4 以及 miR-21 和 CXCR4 同时降低了胶质瘤细胞的迁移、侵袭、增殖，并增强了细胞凋亡，同时在异种移植模型中减少了肿瘤体积和质量。在 miR-21 和 CXCR4 的双靶点敲低组中，抑制作用最强，其下游途径涉及 AKT 轴和 ERK 轴的激活。总之，我们的研究结果表明，miR-21 和 CXCR4 的双靶点敲低可以更有效地抑制移植瘤的增殖、迁移、侵袭和生长，并促进细胞凋亡，这涉及到 PI3K/AKT 和 Raf/MEK/ERK 信号通路。
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