Background:Temozolomide(TMZ)is an important adjuvant chemotherapy drug after glioma surgery.However,with the progress of treatment,most patients will gradually develop drug resistance.Long non-coding RNA(lncRNA)in the...Background:Temozolomide(TMZ)is an important adjuvant chemotherapy drug after glioma surgery.However,with the progress of treatment,most patients will gradually develop drug resistance.Long non-coding RNA(lncRNA)in the prediction and reversal of chemotherapy drug resistance possesses great potential.Methods:1.The clinical data and RNA expression matrix of glioma patients were downloaded from the Chinese Glioma Genome Atlas(CGGA),and the clinical data and RNA expression profiles of 47 patients who only received TMZ chemotherapy after surgery were selected;2.WGCNA was performed on RNA expression profiles to find modules highly correlated with survival time and lncRNAs with high connectivity in modules.Core lncRNA were further screened from the GEO database(P<0.05);survival analysis,correlation analysis,enrichment analysis and co-expression analysis were performed;and 3.A TMZ concentration gradient induced glioma-resistant cells(U251TR).Cell proliferation toxicity assays and real-time quantitative PCR were used to verify the core lncRNA and identify the biological characteristics of U251TR.Results:1.According to the WGCNA analysis,it was found that the pink module is highly correlated with survival time and that there are 17 core lncRNAs with high connectivity in the pink module.2.The expression of the core lncRNA MOCS2-DT in the U251 resistant strain was significantly lower than that in the sensitive strain(P<0.05).3.U251TR cells had significantly larger cell bodies with irregular shapes.U251TR cells had a stronger tolerance to TMZ than U251 cells,and the resistance index was about four times higher(P<0.05).4.The expression levels of MGMT and ABCG2 in U251TR cells were significantly higher than those in parental U251 cells(P<0.05),and the expression levels of MOCS2-DT in U251TR cells were significantly lower than those in parental U251 cells(P<0.05).5.The survival time and survival rate of patients with low expression of MOCS2-DT were significantly lower than those of patients with high expression of MOCS2-DT in patients who only received TMZ chemotherapy after surgery.6.The enrichment analysis results show that the mRNA co-expressed with MOCS2-DT is enriched in synapse organization,regulation of membrane potential and signal release,indicating that MOCS2-DT is closely related to these functions.Conclusion:Targeted regulation of MOCS2-DT may reverse the drug resistance of glioma,improve the prognosis of patients and prolong the survival time of patients.展开更多
文摘Background:Temozolomide(TMZ)is an important adjuvant chemotherapy drug after glioma surgery.However,with the progress of treatment,most patients will gradually develop drug resistance.Long non-coding RNA(lncRNA)in the prediction and reversal of chemotherapy drug resistance possesses great potential.Methods:1.The clinical data and RNA expression matrix of glioma patients were downloaded from the Chinese Glioma Genome Atlas(CGGA),and the clinical data and RNA expression profiles of 47 patients who only received TMZ chemotherapy after surgery were selected;2.WGCNA was performed on RNA expression profiles to find modules highly correlated with survival time and lncRNAs with high connectivity in modules.Core lncRNA were further screened from the GEO database(P<0.05);survival analysis,correlation analysis,enrichment analysis and co-expression analysis were performed;and 3.A TMZ concentration gradient induced glioma-resistant cells(U251TR).Cell proliferation toxicity assays and real-time quantitative PCR were used to verify the core lncRNA and identify the biological characteristics of U251TR.Results:1.According to the WGCNA analysis,it was found that the pink module is highly correlated with survival time and that there are 17 core lncRNAs with high connectivity in the pink module.2.The expression of the core lncRNA MOCS2-DT in the U251 resistant strain was significantly lower than that in the sensitive strain(P<0.05).3.U251TR cells had significantly larger cell bodies with irregular shapes.U251TR cells had a stronger tolerance to TMZ than U251 cells,and the resistance index was about four times higher(P<0.05).4.The expression levels of MGMT and ABCG2 in U251TR cells were significantly higher than those in parental U251 cells(P<0.05),and the expression levels of MOCS2-DT in U251TR cells were significantly lower than those in parental U251 cells(P<0.05).5.The survival time and survival rate of patients with low expression of MOCS2-DT were significantly lower than those of patients with high expression of MOCS2-DT in patients who only received TMZ chemotherapy after surgery.6.The enrichment analysis results show that the mRNA co-expressed with MOCS2-DT is enriched in synapse organization,regulation of membrane potential and signal release,indicating that MOCS2-DT is closely related to these functions.Conclusion:Targeted regulation of MOCS2-DT may reverse the drug resistance of glioma,improve the prognosis of patients and prolong the survival time of patients.
