Objective

This study is to investigate the effects and the mechanisms of mitochondrial ferritin (FtMt) on the glioma tumorigenesis and angiogenesis.

Methods

FtMt expression was detected in glioma tissues and cells as well as in nude mouse tissues. Cell proliferation and apoptosis rate were observed following transfection of LV-FtMt or sh-FtMt in glioma cell line. Moreover, glioma cells with FtMt over-expression/knockdown were co-cultured with human umbilical vein endothelial cells (HUVECs) to observe its function on HUVEC proliferation, angiogenic ability and the vascular endothelial growth factor (VEGF) content. Gain and loss of function of small nucleolar RNA host gene 1 (SNHG1) and miR-9-5p were performed in glioma cells and GBM nude mice to observe its effect on glioma cell proliferation and HUVEC angiogenic ability. Luciferase reporter gene and RIP assay were employed to inspect the interactions among SNHG1, FtMt and miR-9-5p. Additionally, a xenograft mouse model was applied to determine the role of FtMt in glioma.

Results

In this work, FtMt was strongly expressed in glioma tissues and cells as well as in nude mouse tumor tissues. The employment of the loss-of and gain-of functions assays illustrated that FtMt enhanced glioma tumorigenesis and angiogenesis. Mechanistically, our findings showed that FtMt positively related to SNHG1 while negatively correlated with miR-9-5p, and both SNHG1 and FtMt can competitively bind with miR-9-5p. Besides, the inhibition effects of sh-FtMt on glioma were surveyed in vivo experiments.

Conclusion

Evidence in this study suggested that FtMt promotes glioma tumorigenesis and angiogenesis via SNHG1 mediated miR-9-5p expression, which may provide a theoretical basis for glioma treatment.

中文翻译：

---

FtMt 通过 lncRNA SNHG1/miR-9-5p 轴促进神经胶质瘤的肿瘤发生和血管生成。

客观的

本研究旨在探讨线粒体铁蛋白（FtMt）对胶质瘤发生和血管生成的影响及其机制。

方法

在神经胶质瘤组织和细胞以及裸鼠组织中检测到 FtMt 表达。在胶质瘤细胞系中转染LV-FtMt或sh-FtMt后观察细胞增殖和凋亡率。此外，将具有 FtMt 过表达/敲低的神经胶质瘤细胞与人脐静脉内皮细胞 (HUVEC) 共培养，以观察其对 HUVEC 增殖、血管生成能力和血管内皮生长因子 (VEGF) 含量的作用。在胶质瘤细胞和GBM裸鼠中进行小核仁RNA宿主基因1（SNHG1）和miR-9-5p功能的获得和丧失，观察其对胶质瘤细胞增殖和HUVEC血管生成能力的影响。荧光素酶报告基因和 RIP 测定用于检查 SNHG1、FtMt 和 miR-9-5p 之间的相互作用。此外，

结果

在这项工作中，FtMt 在神经胶质瘤组织和细胞以及裸鼠肿瘤组织中强烈表达。使用丧失和获得功能测定表明 FtMt 增强了神经胶质瘤的肿瘤发生和血管生成。从机制上讲，我们的研究结果表明 FtMt 与 SNHG1 呈正相关，而与 miR-9-5p 呈负相关，并且 SNHG1 和 FtMt 均可与 miR-9-5p 竞争结合。此外，在体内实验中考察了sh-FtMt对神经胶质瘤的抑制作用。

结论

本研究中的证据表明，FtMt 通过 SNHG1 介导的 miR-9-5p 表达促进胶质瘤的发生和血管生成，这可能为胶质瘤的治疗提供理论依据。