Long Non-Coding RNA MALAT1 Decreases the Sensitivity of Resistant Glioblastoma Cell Lines to Temozolomide.

Abstract

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.

• Authors: Hongwei Li, Xiaoli Yuan, Dongming Yan, Dongpeng Li, Fangxia Guan, Yang Dong, Hao Wang, Xianzhi Liu, Bo Yang
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 42 Issue 3 Pg. 1192-1201 ( 2017) ISSN: 1421-9778 [Electronic] Germany
• PMID: 28668966 (Publication Type: Journal Article)
• Copyright: © 2017 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Antineoplastic Agents, Alkylating
• MALAT1 long non-coding RNA, human
• RNA, Long Noncoding
• ZEB1 protein, human
• Zinc Finger E-box-Binding Homeobox 1
• Dacarbazine
• Temozolomide

Topics

• Antineoplastic Agents, Alkylating (pharmacology)
• Brain (drug effects, metabolism, pathology)
• Brain Neoplasms (drug therapy, genetics, pathology)
• Cell Line, Tumor
• Dacarbazine (analogs & derivatives, pharmacology)
• Drug Resistance, Neoplasm
• Epithelial-Mesenchymal Transition (drug effects)
• Gene Expression Regulation, Neoplastic
• Glioblastoma (drug therapy, genetics, pathology)
• Humans
• RNA, Long Noncoding (genetics)
• Temozolomide
• Up-Regulation
• Zinc Finger E-box-Binding Homeobox 1 (genetics)