Objective To investigate whether the competitive endogenous RNA (ceRNA) regulatory network is associated with the progression risk of low-grade glioma (LGG), and identify potential long non-coding RNA (lncRNA) biomarkers, such as TDRG1, for functional studies and evaluation in LGG.
Methods Using transcriptomic, genomic, and clinical data from 530 samples in The Cancer Genome Atlas (TCGA), 198 samples in the Chinese Glioma Genome Atlas (CGGA), and 3 samples from the Guangxi Medical University Cancer Hospital, along with experimental validation, we comprehensively analyzed significantly differentially expressed genes (DEGs) in patients with LGG progression. Based on the DEGs, we constructed an lncRNA-miRNA-messenger RNA (mRNA) network and performed functional analysis of candidate lncRNAs using bioinformatics methods. Subsequently, we employed a virus-based approach to establish a high-precision C57BL/6J mouse glioma model for in vivo functional validation.
Results A total of 35 progression-related DEGs were identified in LGG and their functions were enriched in signal peptides and immune pathways. The differential expression index was significantly associated with mutations in IDH1, TP53, PTEN, EGFR, and CDKN2A (P < 0.05). The ceRNA network analysis revealed that lncRNAs such as TDRG1 regulated progression of glioma by targeting miR-30 and miR- 513. Survival analysis showed that the up-regulation of miR-30, miR-1254, and TDRG1 significantly shortened the survival time (P < 0.05). RNA sequencing and qPCR confirmed the specific overexpression of TDRG1 in LGG (P < 0.05). In a mouse model, TDRG1 significantly promoted glioma growth (P < 0.05), indicating its core role in LGG progression.
Conclusion TDRG1 is significantly associated with the progression of LGG, meriting further exploration of its functional and clinical significance in low-grade glioma.
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