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鉴定一种新型环状 RNA circZNF652/miR-486-5p/SERPINE1 信号级联,调节胶质母细胞瘤 (GBM) 中的癌症侵袭性。

Identification of a novel circular RNA circZNF652/miR-486-5p/SERPINE1 signaling cascade that regulates cancer aggressiveness in glioblastoma (GBM).

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Shenzhen University (People's Hospital of Shenzhen Baoan District), Shenzhen, Guang Dong, China.

Department of Endocrinology, The Second Affiliated Hospital of Shenzhen University (People's Hospital of Shenzhen Baoan District), Shenzhen, Guang Dong, China.

出版信息

Bioengineered. 2022 Jan;13(1):1411-1423. doi: 10.1080/21655979.2021.2018096.

Abstract

Circular RNAs (circRNAs) are closely associated with cancer development in glioblastoma (GBM), and this study aims to explore the molecular mechanisms of a novel circular RNA circZNF652 in regulating GBM aggressiveness. The present study found that CircZNF652 and SERPINE1 were upregulated, while miR-486-5p was downregulated in GBM tissues and cell lines, and GBM patients with high expression of CircZNF652 and SERPINE1, and patients with low expression of miR-486-5p tended to have a worse prognosis. Further results validated that both silencing of circZNF652 and miR-486-5p overexpression suppressed cell growth, migration, invasion, epithelial-mesenchymal transition (EMT) and tumorigenesis in GBM cells and . Next, the underlying mechanisms were investigated, and we found that circZNF652 sponged miR-486-5p to upregulate SERPINE1 in GBM cells. Also, we validated that knock-down of circZNF652 regulated the miR-486-5p/SERPINE1 axis to reverse the malignant phenotypes in GBM cells. Interestingly, we noticed that GBM cells derived exosomes were characterized by high-expressed CircZNF652. Collectively, we concluded that targeting the circular RNA circZNF652/miR-486-5p/SERPINE1 axis was a novel and effective strategy to suppress cancer progression in GBM.

摘要

环状 RNA(circRNAs)与脑胶质瘤(GBM)的发生发展密切相关,本研究旨在探讨新型环状 RNA circZNF652 调节 GBM 侵袭性的分子机制。本研究发现,circZNF652 和 SERPINE1 在 GBM 组织和细胞系中上调,而 miR-486-5p 下调,GBM 患者中 circZNF652 和 SERPINE1 表达高,miR-486-5p 表达低的患者预后较差。进一步的结果验证了沉默 circZNF652 和过表达 miR-486-5p 均可抑制 GBM 细胞的生长、迁移、侵袭、上皮间质转化(EMT)和肿瘤生成。接下来,研究了潜在的机制,发现 circZNF652 海绵吸附 miR-486-5p 上调 GBM 细胞中的 SERPINE1。此外,还验证了敲低 circZNF652 调节 miR-486-5p/SERPINE1 轴逆转 GBM 细胞的恶性表型。有趣的是,我们注意到 GBM 细胞衍生的外泌体具有高表达的 CircZNF652。综上所述,靶向环状 RNA circZNF652/miR-486-5p/SERPINE1 轴是抑制 GBM 进展的一种新的有效策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77c/8805984/4357b2ab77dc/KBIE_A_2018096_F0001_OC.jpg

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