Association Between Temozolomide Resistance and Long Non-Coding RNA Expression Profiles in Glioblastoma Cell Lines

Background: Glioblastoma (GBM) is the most aggressive primary brain tumour in adults and is characterised by poor prognosis and frequent resistance to temozolomide (TMZ)-based chemotherapy. Increasing evidence suggests that long non-coding RNAs (lncRNAs) contribute to GBM progression, therapeutic adaptation, and chemoresistance. This study investigated the relationship between TMZ responsiveness and the expression of selected lncRNAs in GBM cell lines exhibiting distinct sensitivity profiles. Methods: Human GBM cell lines (A172, U87, and T98G) and normal human astrocytes (NHA) were exposed to TMZ for 24-72 h. Cell viability, cell cycle distribution, MGMT protein expression, and expression levels of nine selected lncRNAs were analysed using MTT assay, flow cytometry, Western blot, and quantitative RT-PCR, respectively. Results: TMZ induced dose- and time-dependent reductions in cell viability in all analysed cell lines. A172 cells exhibited the greatest TMZ sensitivity, whereas T98G cells displayed the highest resistance. TMZ-sensitive GBM cells demonstrated pronounced G2/M cell cycle arrest, while T98G cells showed minimal cell cycle perturbation. MGMT protein expression was markedly elevated in T98G cells and decreased following exposure to higher TMZ concentrations. Distinct lncRNA expression profiles were identified among GBM cell lines. MALAT1 expression was consistently reduced, whereas NCK1-AS1 was strongly upregulated, particularly in T98G cells. TMZ exposure induced significant alterations in H19, PVT1, OIP5-AS1, and NCK1-AS1 expression, suggesting their potential involvement in adaptive resistance mechanisms. Conclusions: Collectively, these findings indicate that selected lncRNAs, particularly H19, MALAT1, NCK1-AS1, and PVT1, may contribute to TMZ resistance in GBM and could be promising biomarkers and therapeutic targets for precision oncology approaches.