1. Academic Validation
  2. NCK1-AS1 Increases Drug Resistance of Glioma Cells to Temozolomide by Modulating miR-137/ TRIM24

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

  • Cancer Biother Radiopharm. 2020 Mar;35(2):101-108. doi: 10.1089/cbr.2019.3054.
Mingsheng Chen 1 Yingying Cheng 1 Zhihai Yuan 1 Fenglu Wang 1 Lei Yang 1 Haikang Zhao 1
Affiliations

Affiliation

  • 1 Department of Neurosurgery, The Second Affiliated Hospital of Xi'an Medical University, Xi'an City, China.
Abstract

Background: 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. Methods: 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, in situ 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 TRIM24 and miR-137 was confirmed by dual luciferase activity assay. Results: 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 TRIM24 expression. Then, expression of miR-137 alleviated the NCK1-AS1 overexpression-induced increased expression of TRIM24. In addition, the decreases of cell viability and IC50 induced by NCK1-AS1 knockdown were reversed after adding TRIM24 in U251/TMZ and A172/TMZ cells. Conclusion: NCK1-AS1 could increase drug resistance of glioma cells to TMZ by modulating miR-137/TRIM24 pathway.

Keywords

NCK1-AS1; TRIM24; glioma; miR-137; temozolomide.

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