The LINC00957/miR-17-5p axis regulates the cell cycle and migration in glioblastoma via the cuproptosis-related gene nephronectin.

Background: Glioblastoma (GBM) is characterized by poor prognosis and a high malignancy. The competing endogenous RNA (ceRNA) network formed by long non-coding RNA (lncRNA) and microRNA (miRNA) can regulate the incidence of GBM. Therapeutic strategies targeting cuproptosis-related genes (CRGs) have helped reduce drug resistance in patients. However, the regulatory mechanism underlying the ceRNA network related to cuproptosis in GBM remains unclear. Therefore, we aim to explore the ceRNA regulatory axis associated with cuproposis in GBM and provide a new protocol for therapy.

Methods: The ceRNA network related to CRG was constructed by bioinformatics. Dual-luciferase reporter assay and other experiments were used to prove the conclusion.

Results: We found that the LINC00957/miR-17-5p axis drove nephronectin (NPNT) expression to promote the malignant progression of GBM. First, by measuring the copper ion concentration and reactive oxygen species (ROS) levels, we found that inhibiting NPNT could promote cuproptosis. Meanwhile, the results of enrichment analysis and phenotypic experiments demonstrated that the LINC00957/miR-17-5p/NPNT axis can regulate the cell cycle and migration in GBM. In terms of mechanistic evidence, findings from reporter gene experiments suggested that LINC00957 acted as a ceRNA to regulate the expression of NPNT via miR-17-5p. In addition, findings from rescue experiments confirmed that the regulation of malignant GBM progression by LINC00957 depended on NPNT to an extent.

Conclusions: Our findings indicate that the ceRNA regulatory network is related to cuproptosis in GBM and provide novel potential targets for the diagnosis and treatment of GBM.