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Long Non-Coding RNA MALAT1 Decreases the Sensitivity of Resistant Glioblastoma Cell Lines to Temozolomide
Hongwei Li1, Xiaoli Yuan2, Dongming Yan1
1Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Background/Aim:
Multidrug resistance (MDR) is largely responsible for the failure of chemotherapy. The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript (MALAT1) has been reported to be closely related to tumor biology. In the present study, whether MALAT1 contributes to the resistance of glioblastoma cell lines to temozolomide (TMZ) was investigated.
Methods:
The glioblastoma cell lines U251 and U87 were exposed to increasing concentrations of TMZ to generate TMZ-resistant colonies (the U251/TMZ and U87/TMZ cell lines). The expression levels of MALAT1 and proteins related to epithelial-mesenchymal transition (EMT) were detected by real-time PCR and western blot, respectively. After the transfection of si-MALAT1 or pcDNA-MALAT1, cell viability, mRNA expression of MDR-associated proteins (MDR1, MRP5 and LRP1), and protein expression of EMT related proteins (ZEB1, Snail and SLUG) were evaluated.
Results:
The expression of MALAT1 was upregulated in the U251/TMZ and U87/TMZ cell lines compared to that in U251 and U87 cell lines, respectively. The treatment of si-MALAT1 decreased MDR1, MRP5, and LRP1 expression, enhanced cell sensitivity to TMZ, and downregulated ZEB1 protein expression, whereas pcDNA-MALAT1 had the opposite effects. However, the effects of si-MALAT1 on MDR -associated protein expression, cell viability, and EMT status were reversed by the transfection of pcDNA-ZEB1, and the effects of pcDNA-MALAT1 were reversed by the transfection of si-ZEB1. In vivo, MALAT1 overexpression enhanced tumors' TMZ resistance and upregulated ZEB1 expression.
Conclusion:
MALAT1 decreased the sensitivity of resistant glioma cell lines to TMZ by regulating ZEB1.
Insights
The long non-coding RNA MALAT1 promotes glioblastoma resistance to temozolomide (TMZ) by upregulating ZEB1. Inhibiting MALAT1 can restore sensitivity to chemotherapy in resistant glioblastoma cells.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multidrug resistance (MDR) is a major challenge in chemotherapy, leading to treatment failure.
- Long non-coding RNAs (lncRNAs) like MALAT1 are implicated in tumor biology and drug resistance.
- Glioblastoma remains a challenging cancer with limited treatment options.
Purpose of the Study:
- To investigate the role of MALAT1 in temozolomide (TMZ) resistance in glioblastoma cell lines.
- To determine the molecular mechanisms by which MALAT1 influences TMZ resistance and epithelial-mesenchymal transition (EMT).
Main Methods:
- Glioblastoma cell lines (U251, U87) were adapted to temozolomide (TMZ) to create resistant cell lines.
- Expression levels of MALAT1 and EMT-related proteins were assessed using real-time PCR and western blot.
- Functional studies involved transfecting cells with si-MALAT1 or pcDNA-MALAT1 and evaluating cell viability, MDR-associated protein expression, and EMT markers.
Main Results:
- MALAT1 expression was significantly upregulated in TMZ-resistant glioblastoma cells.
- si-MALAT1 treatment decreased MDR protein expression, enhanced TMZ sensitivity, and downregulated ZEB1.
- ZEB1 mediated the effects of MALAT1 on MDR and EMT, both in vitro and in vivo.
Conclusions:
- MALAT1 contributes to TMZ resistance in glioblastoma by upregulating ZEB1.
- Targeting MALAT1 may represent a therapeutic strategy to overcome chemotherapy resistance in glioblastoma.
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