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Downregulation of hsa_circ_0000936 sensitizes resistant glioma cells to temozolomide by sponging miR-1294
Journal of Biosciences ( IF 2.9 ) Pub Date : 2020-07-24 , DOI: 10.1007/s12038-020-00072-z
Lin Hua , Lifa Huang , Xin Zhang , Haoke Feng

Glioma is one of the most aggressive forms of brain tumor and is hallmarked by high rate of mortality, metastasis and drug resistance. Herein, we explore the role of circular RNA (circRNA) hsa_circ_0000936 in the resistance of glioma cells to temozolomide (TMZ). In this study, Relative changes in gene expression levels were compared using qRT-PCR. The role of hsa_circ_0000936 was characterized by cell count kit -8 assay and flow cytometry. Luciferase reporter assay was carried out for target validation.We found that hsa_circ_0000936 was upregulated in glioma tissues as compared to their adjacent normal tissues. Increased expression of hsa_circ_0000936 was found in the glioma tissues of patients showing resistance to TMZ compared with that of patients showing sensitivity to TMZ. The upregulation of hsa_circ_0000936 was also confirmed in TMZ-resistant glioma cells. miR-1294 was downregulated in TMZ-resistant glioma cells and identified as a direct target of hsa_circ_0000936. Downregulation of hsa_circ_0000936 increased the sensitivity of TMZ-resistant glioma cells towards TMZ. Moreover, restoration of miR-1294 could abrogate the promoting effect of hsa_circ_0000936 on TMZ resistance in TMZ-resistant glioma cells. In conclusion, downregulation of hsa_circ_0000936 sensitizes TMZ-resistant glioma cells to TMZ by sponging miR-1294, suggesting that hsa_circ_0000936 may be a potential target for overcoming the resistance of glioma cells to TMZ.

中文翻译:

hsa_circ_0000936 的下调通过海绵 miR-1294 使抗性神经胶质瘤细胞对替莫唑胺敏感

神经胶质瘤是最具侵袭性的脑肿瘤形式之一,其特点是死亡率高、转移率高和耐药性高。在此,我们探讨了环状 RNA (circRNA) hsa_circ_0000936 在神经胶质瘤细胞对替莫唑胺 (TMZ) 抗性中的作用。在本研究中,使用 qRT-PCR 比较了基因表达水平的相对变化。hsa_circ_0000936的作用通过细胞计数试剂盒-8测定和流式细胞术表征。进行荧光素酶报告基因检测以进行靶标验证。我们发现,与其相邻的正常组织相比,胶质瘤组织中的 hsa_circ_0000936 上调。与对 TMZ 敏感的患者相比,在对 TMZ 有抗性的患者的胶质瘤组织中发现 hsa_circ_0000936 的表达增加。在 TMZ 抗性神经胶质瘤细胞中也证实了 hsa_circ_0000936 的上调。miR-1294 在 TMZ 抗性神经胶质瘤细胞中下调,并被确定为 hsa_circ_0000936 的直接靶标。hsa_circ_0000936 的下调增加了 TMZ 抗性神经胶质瘤细胞对 TMZ 的敏感性。此外,miR-1294的恢复可以消除hsa_circ_0000936对TMZ抗性神经胶质瘤细胞中TMZ抗性的促进作用。总之,hsa_circ_0000936 的下调通过海绵 miR-1294 使 TMZ 抗性神经胶质瘤细胞对 TMZ 敏感,表明 hsa_circ_0000936 可能是克服神经胶质瘤细胞对 TMZ 抗性的潜在靶点。hsa_circ_0000936 的下调增加了 TMZ 抗性神经胶质瘤细胞对 TMZ 的敏感性。此外,miR-1294的恢复可以消除hsa_circ_0000936对TMZ抗性神经胶质瘤细胞中TMZ抗性的促进作用。总之,hsa_circ_0000936 的下调通过海绵 miR-1294 使 TMZ 抗性神经胶质瘤细胞对 TMZ 敏感,表明 hsa_circ_0000936 可能是克服神经胶质瘤细胞对 TMZ 抗性的潜在靶点。hsa_circ_0000936 的下调增加了 TMZ 抗性神经胶质瘤细胞对 TMZ 的敏感性。此外,miR-1294的恢复可以消除hsa_circ_0000936对TMZ抗性神经胶质瘤细胞中TMZ抗性的促进作用。总之,hsa_circ_0000936 的下调通过海绵 miR-1294 使 TMZ 抗性神经胶质瘤细胞对 TMZ 敏感,表明 hsa_circ_0000936 可能是克服神经胶质瘤细胞对 TMZ 抗性的潜在靶点。
更新日期:2020-07-24
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