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miR-720 is a key regulator of glioma migration and invasion by controlling TARSL2 expression
Human Cell ( IF 3.4 ) Pub Date : 2021-05-23 , DOI: 10.1007/s13577-021-00551-x
Yinlong Liu 1 , Kuan Jiang 2 , Tongle Zhi 3 , Xiupeng Xu 4
Affiliation  

Glioblastoma (GBM) is the most lethal type of primary brain tumor and is characterized by diffuse infiltrative growth. However, the mechanisms that control this phenotype remain largely unknown. Emerging evidence has demonstrated that the abnormal expression of microRNAs and their target genes are involved in the migration and invasion of glioma cells. In this study, we demonstrated that microRNA-720 (miR-720) was significantly upregulated in glioma tissues and cells. Functional experiments showed that overexpression of miR-720 promotes glioma migration and invasion, while downregulation of miR-720 inhibits glioma migration and invasion. Meanwhile, we found that threonyl-tRNA synthetase like-2 (TARSL2) was a direct and functional target of miR-720 in glioma. Reintroduction of TARSL2 into glioma cells repressed the invasion promoting function of miR-720, whereas downregulation of TARSL2 reversed the anti-invasion function of anti-miR-720. Furthermore, quantitative real-time polymerase chain reaction results showed that miR-720 was inversely correlated with TARSL2 expression in 40 GBM tissues. Finally, in vivo experiments showed that miR-720 promotes glioma growth and upregulates invasion-related genes in nude mice. Overall, our findings suggest increasing miR-720 enhances glioma migration and invasion through downregulation of TARSL2, which may provide novel insight into the treatment of glioma.



中文翻译:

miR-720 是胶质瘤迁移和侵袭的关键调节因子,通过控制 TARSL2 表达

胶质母细胞瘤 (GBM) 是最致命的原发性脑肿瘤类型,其特征是弥漫性浸润性生长。然而,控制这种表型的机制在很大程度上仍然未知。新出现的证据表明,microRNAs及其靶基因的异常表达参与了胶质瘤细胞的迁移和侵袭。在这项研究中,我们证明了 microRNA-720 (miR-720) 在神经胶质瘤组织和细胞中显着上调。功能实验表明,miR-720的过表达促进了胶质瘤的迁移和侵袭,而miR-720的下调则抑制了胶质瘤的迁移和侵袭。同时,我们发现苏氨酰-tRNA 合成酶样 2 (TARSL2) 是 miR-720 在胶质瘤中的直接和功能靶点。将 TARSL2 重新引入神经胶质瘤细胞抑制了 miR-720 的侵袭促进功能,而 TARSL2 的下调逆转了抗 miR-720 的抗侵袭功能。此外,定量实时聚合酶链反应结果显示 miR-720 与 40 个 GBM 组织中的 TARSL2 表达呈负相关。最后,体内实验表明,miR-720促进裸鼠胶质瘤生长并上调侵袭相关基因。总体而言,我们的研究结果表明,增加 miR-720 可通过下调 TARSL2 增强神经胶质瘤的迁移和侵袭,这可能为神经胶质瘤的治疗提供新的见解。定量实时聚合酶链反应结果显示,40 个 GBM 组织中 miR-720 与 TARSL2 表达呈负相关。最后,体内实验表明,miR-720促进裸鼠胶质瘤生长并上调侵袭相关基因。总体而言,我们的研究结果表明,增加 miR-720 可通过下调 TARSL2 增强神经胶质瘤的迁移和侵袭,这可能为神经胶质瘤的治疗提供新的见解。定量实时聚合酶链反应结果显示,40 个 GBM 组织中 miR-720 与 TARSL2 表达呈负相关。最后,体内实验表明,miR-720促进裸鼠胶质瘤生长并上调侵袭相关基因。总体而言,我们的研究结果表明,增加 miR-720 可通过下调 TARSL2 增强神经胶质瘤的迁移和侵袭,这可能为神经胶质瘤的治疗提供新的见解。

更新日期:2021-05-23
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