Facilitation of Temozolomide Resistance of Glioblastoma by Long Noncoding RNA DLK1-35

Abstract

Background: Long noncoding RNAs played critical roles in glioblastoma development. Objectives: This study aimed to examine the impacts of lncRNA DLK1-35 on glioblastoma cells and mice. Methods: Methyl Thiazolyl Tetrazolium (MTT) was applied for examining the viabilities of U87 and U251 cells, as well as IC50 values of temozolomide (TMZ). LncRNA DLK1-35 expressions were detected using RT-qPCR. Proliferation and apoptosis of TMZ-resistant U251 (U251 TR) cells were evaluated using colony formation and flow cytometry, respectively. Western blot was applied to analyze O6-methylguanine-DNA methyltransferase (MGMT) protein expressions. The xenograft model was used for detecting the weight and volume of tumors in mice. Results: TMZ treatment suppressed the viabilities of glioblastoma cells dose-dependently. Moreover, TMZ-resistant glioblastoma cells had higher IC50 values. lncRNA DLK1-35 was upregulated in TMZ-resistant cells while the suppression of lncRNA DLK1-35 caused low proliferation and a higher apoptosis rate. Moreover, MGMT was also inhibited by lncRNA DLK1-35 downregulation. Additionally, the weight and volume of tumors in mice were also inhibited with the knockdown of lncRNA DLK1-35. Conclusion: Knockdown of lncRNA DLK1-35 inhibited MGMT to decrease the TMZ resistance in vitro and in vivo in glioblastoma.