FXR1 promotes glioma progression by downregulating microRNA-124-3p through long noncoding RNA FGD5-AS1 upregulation

• Published in: Acta neurologica Belgica 2023-08, Vol.123 (4), p.1453-1464
• Main Authors: Gong, Xin, Huang, Mengyi, Chen, Lei, Zeng, Huan
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Medicine/Public Health; Neurology; Neuroradiology; Neurosciences; Original Article
• ISSN: 0300-9009; 2240-2993
• DOI: 10.1007/s13760-023-02263-5

Objective 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. Methods 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. Results 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. Conclusion FXR1 might act as an oncogene in gliomas by declining miR-124-3p through FGD5-AS1.