Department of Neurosurgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan, People's Republic of China.
Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61, West Jiefang Road, Furong District, Changsha, 410005, Hunan, People's Republic of China.
Acta Neurol Belg. 2023 Aug;123(4):1453-1464. doi: 10.1007/s13760-023-02263-5. Epub 2023 Apr 19.
As reported, glioma progression is affected by altered FXR1, long non-coding RNA FGD5-AS1, and microRNA (miR)-124-3p. However, relationships among these genes remain unclear. Accordingly, this paper ascertains whether FXR1 manipulates glioma progression via the FGD5-AS1/miR-124-3p axis.
Glioma tissues were harvested, in which FGD5-AS1 and miR-124-3p levels were examined with qRT-PCR and FXR1 level was assessed with qRT-PCR and western blot. The interaction of miR-124-3p with FGD5-AS1 was analyzed by dual-luciferase reporter, RIP, and Pearson correlation coefficient assays, and that of FXR1 with FGD5-AS1 was assessed by RIP and Pearson correlation coefficient assays. Glioma cells were obtained, followed by qRT-PCR detection of miR-124-3p expression. After gain- or loss-of-function assays, EdU, Transwell, and tubule formation assays were performed to determine cell proliferation, invasion and migration, and angiogenesis. Next, the intracranial in situ graft tumor model was established for in vivo verification.
FGD5-AS1 and FXR1 levels were high, but miR-124-3p level was low in glioma tissues. Likewise, glioma cells had downregulated miR-124-3p expression. Mechanistically, FGD5-AS1 negatively bound to miR-124-3p, and FXR1 was positively correlated and interacted with FGD5-AS1. miR-124-3p overexpression or FGD5-AS1 or FXR1 knockdown restricted cell invasion, proliferation, migration, and angiogenesis in gliomas. miR-124-3p inhibition abrogated the repressive impacts of FXR1 knockdown on the malignant progression of gliomas. Also, FXR1 constrained tumor growth and angiogenesis in mice, which was counterweighed by inhibiting miR-124-3p.
FXR1 might act as an oncogene in gliomas by declining miR-124-3p through FGD5-AS1.
据报道，FGD5-AS1 长链非编码 RNA 和 microRNA（miR）-124-3p 的改变会影响神经胶质瘤的进展。然而，这些基因之间的关系尚不清楚。因此，本文旨在确定 FXR1 是否通过 FGD5-AS1/miR-124-3p 轴来调控神经胶质瘤的进展。
收集神经胶质瘤组织，采用 qRT-PCR 检测 FGD5-AS1 和 miR-124-3p 的水平，采用 qRT-PCR 和 Western blot 检测 FXR1 的水平。采用双荧光素酶报告、RIP 和 Pearson 相关系数分析检测 miR-124-3p 与 FGD5-AS1 的相互作用，采用 RIP 和 Pearson 相关系数分析检测 FXR1 与 FGD5-AS1 的相互作用。获得神经胶质瘤细胞，采用 qRT-PCR 检测 miR-124-3p 的表达。通过 gain-或 loss-of-function 测定后，进行 EdU、Transwell 和管形成测定以确定细胞增殖、侵袭和迁移以及血管生成。接下来，建立颅内原位移植肿瘤模型进行体内验证。
FGD5-AS1 和 FXR1 的水平在神经胶质瘤组织中较高，而 miR-124-3p 的水平较低。同样，神经胶质瘤细胞中 miR-124-3p 的表达下调。在机制上，FGD5-AS1 负向结合 miR-124-3p，而 FXR1 与 FGD5-AS1 呈正相关并相互作用。miR-124-3p 过表达或 FGD5-AS1 或 FXR1 敲低限制了神经胶质瘤的侵袭、增殖、迁移和血管生成。miR-124-3p 的抑制消除了 FXR1 敲低对神经胶质瘤恶性进展的抑制作用。此外，FXR1 抑制了小鼠肿瘤的生长和血管生成，而抑制 miR-124-3p 则抵消了这一作用。
FXR1 可能通过 FGD5-AS1 降低 miR-124-3p 来发挥神经胶质瘤中的致癌基因作用。
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