Over-expression of lncRNA TMEM161B-AS1 promotes the malignant biological behavior of glioma cells and the resistance to temozolomide via up-regulating the expression of multiple ferroptosis-related genes by sponging hsa-miR-27a-3p.

Over-expression of lncRNA TMEM161B-AS1 promotes the malignant biological behavior of glioma cells and the resistance to temozolomide via up-regulating the expression of multiple ferroptosis-related genes by sponging hsa-miR-27a-3p.
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lncRNA TMEM161B-AS1的过表达通过海绵hsa-miR-27a-3p上调多个铁死亡相关基因的表达促进胶质瘤细胞的恶性生物学行为和对替莫唑胺的耐药性

DOI:
10.1038/s41420-021-00709-4
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发表时间:
2021-10-23
影响因子:
7
通讯作者:
Lin Y
Lin Y
中科院分区:
医学2区
文献类型:
--
作者:
Chen Q;Wang W;Wu Z;Chen S;Chen X;Zhuang S;Song G;Lv Y;Lin Y

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越来越多的证据表明,长链非编码RNA(lncRNA)在胶质母细胞瘤(GBM)细胞的恶性生物学行为和耐药性中起重要作用。本研究分析了lncRNA TMEM 161 B-AS 1在GBM细胞恶性生物学行为和替莫唑胺(TMZ)耐药中的作用及其可能机制。研究发现FANCD 2和CD 44与GBM的发生、TMZ耐药及GBM患者的生存期显著相关。TMEM 161 B-AS 1基因的敲除可通过海绵状hsa-miR-27 a-3 p下调FANCD 2和CD 44的表达,抑制U87和U251细胞的增殖、迁移、侵袭,促进细胞凋亡和铁凋亡。下调lncRNA TMEM 161 B-AS 1和/或过表达hsa-miR-27 a-3 p可下调FANCD 2和CD 44的表达,抑制裸鼠肿瘤生长。这些结果表明lncRNA TMEM 161 B-AS 1-hsa-miR-27 a-3 p-FANCD 2/CD 44信号轴调控GBM的恶性生物学行为和TMZ耐药。这些发现有望为胶质瘤的治疗提供有希望的治疗靶点。
A growing body of evidence suggests that long-chain non-coding RNA (lncRNA) plays an important role in the malignant biological behavior and drug resistance of glioblastoma (GBM) cells. In this study, we analyzed the role and potential mechanism of lncRNA TMEM161B-AS1 in the malignant biological behavior of GBM cells and temozolomide (TMZ) resistance. Studies have found that FANCD2 and CD44 are significantly related to the occurrence of GBM, TMZ resistance and the survival of GBM patients. Knockdown of TMEM161B-AS1 down-regulated the expression of FANCD2 and CD44 by sponging hsa-miR-27a-3p, inhibited the proliferation, migration, invasion and promoted apoptosis, ferroptosis of U87 cells and U251 cells. Down-regulation of lncRNA TMEM161B-AS1 and/or over-expression of hsa-miR-27a-3p down-regulated the expression of FANCD2 and CD44, and inhibited the tumor growth in nude mice. These results demonstrated that the lncRNA TMEM161B-AS1-hsa-miR-27a-3p-FANCD2/CD44 signal axis regulated the malignant biological behavior of GBM and TMZ resistance. These findings were expected to provide promising therapeutic targets for the treatment of glioma.
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