NCK1-AS1 Increases Drug Resistance of Glioma Cells to Temozolomide by Modulating miR-137/ <i>TRIM24</i>

Abstract

<b><i>Background:</i></b> Glioma is a common malignant tumor. The purpose of this study was to investigate the effect and molecular mechanism of long noncoding RNA (lncRNA) NCK1-AS1 on the drug resistance of temozolomide (TMZ) in glioma cells. <b><i>Methods:</i></b> The fresh and recurrent glioma tissues and peritumoral brain edema (PTBE) were collected from the same patient. U251 and A172 cells were treated with TMZ to screen TMZ-resistant cells. The expression levels of NCK1-AS1, miR-137, or TRIM24 were detected by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, <i>in situ</i> hybridization (ISH), or RNA pull-down assay. Cell viability was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazoliumbromide (MTT) assay. In addition, the relationship between NCK1-AS1 and miR-137 or <i>TRIM24</i> and miR-137 was confirmed by dual luciferase activity assay. <b><i>Results:</i></b> NCK1-AS1 expression was increased in regular and recurrent glioma tissues and TMZ-resistant cells. Cell viability was increased in TMZ-resistant cells, and the IC50 of TMZ also increased in TMZ resistant cells. However, knockdown of NCK1-AS1 inhibited these increases. Moreover, suppression of NCK1-AS1 increased miR-137 expression, whereas overexpression of miR-137 decreased <i>TRIM24</i> expression. Then, expression of miR-137 alleviated the NCK1-AS1 overexpression-induced increased expression of <i>TRIM24</i>. In addition, the decreases of cell viability and IC50 induced by NCK1-AS1 knockdown were reversed after adding <i>TRIM24</i> in U251/TMZ and A172/TMZ cells. <b><i>Conclusion:</i></b> NCK1-AS1 could increase drug resistance of glioma cells to TMZ by modulating miR-137/<i>TRIM24</i> pathway.