Circular RNA circLGMN facilitates glioblastoma progression by targeting miR-127-3p/LGMN axis
Circular RNA circLGMN facilitates glioblastoma progression by targeting miR-127-3p/LGMN axis
复制标题
环状RNA circLGMN通过靶向miR-127-3p/LGMN轴促进胶质母细胞瘤进展
DOI：
10.1016/j.canlet.2021.09.030
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发表时间：
2021-09-28
期刊：
影响因子：
9.7
通讯作者：
Qiu, Yongming
中科院分区：
文献类型：
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作者：
Chen, Binghong;Wang, Mengying;Qiu, Yongming
胶质母细胞瘤（GBM）是最具破坏性的癌症之一，其特征在于快速的细胞增殖和侵袭性。Legumain（LGMN）是一种基质特异性蛋白酶，与GBM进展不良相关。环状RNA（circRNA）在各种癌症中异常表达，并在肿瘤进展中起关键作用;然而，源自LGMN的circRNA的功能作用在GBM中仍然很大程度上未知。在此，我们发现hsa_circ_0033009（circLGMN）是最丰富表达的源自LGMN的circRNA。CircLGMN在高级别胶质瘤（HGG）中上调，并且circLGMN的高表达与胶质瘤患者的不良预后相关。CircLGMN过表达促进GBM细胞增殖和增强细胞侵袭。从机制上讲，circLGMN充当miR-127- 3 p的海绵，并阻止miR-127- 3 p介导的LGMN mRNA降解，最终导致LGMN蛋白表达增加。用miR-127- 3 p模拟物处理抑制了过表达circLGMN的GBM细胞的增殖并降低了侵袭。此外，circLGMN过表达促进体内GBM恶性肿瘤，而miR-127- 3 p过表达减轻了这种作用。综上所述，circLGMN是一种新的促肿瘤circRNA，其通过海绵状作用于miR 127 - 3 p，最终导致LGMN上调。因此，靶向circLGMN/miR-127- 3 p/LGMN轴可能是GBM治疗的有希望的策略。更重要的是，circLGMN对LGMN表达的自我调节机制的发现，将有助于对LGMN的进一步研究。
Glioblastoma (GBM) is one of the most devastating cancers and is characterized by rapid cell proliferation and aggressive invasiveness. Legumain (LGMN), a substrate-specific protease, is associated with poor progression of GBM. Circular RNAs (circRNAs) are aberrantly expressed in various cancers and play crucial roles in tumor progression; however, the functional roles of circRNAs originating from LGMN remain largely unknown in GBM. Herein, we found that hsa_circ_0033009 (circLGMN) was the most abundantly expressed circRNA derived from LGMN. CircLGMN was upregulated in high-grade glioma (HGG), and high expression of circLGMN was associated with poor prognosis in patients with glioma. CircLGMN overexpression promoted GBM cell proliferation and enhanced cell invasion. Mechanistically, circLGMN acts as a sponge for miR-127-3p, and prevents miR-127-3pmediated degradation of LGMN mRNA, ultimately leading to increased LGMN protein expression. Treatment with miR-127-3p mimic suppressed proliferation and reduced invasion of GBM cells overexpressing circLGMN. Moreover, circLGMN overexpression promoted GBM malignancy in vivo, while miR-127-3p overexpression alleviated this effect. Taken together, circLGMN is a novel tumor-promoting circRNA that acts by sponging miR127-3p, which ultimately leads to LGMN upregulation. Thus, targeting the circLGMN/miR-127-3p/LGMN axis might be a promising strategy for GBM treatment. More importantly, the discovery of the self-regulatory mechanism of LGMN expression by circLGMN, will facilitate further research on LGMN.