MiRNA-451通过mTOR/HIF-1α/VEGF信号通路靶向CAB39抑制胶质瘤细胞增殖和侵袭

Yang Nan, Hongbao Guo, Liyun Guo, Le Wang, Bingcheng Ren, Kai Yu, Qiang Huang, Yue Zhong
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引用次数: 53

摘要

MicroRNAs (miRNAs)广泛表达并调控着大多数生物功能。根据几个研究组的研究,miR-451在胶质瘤细胞中的表达降低。先前的研究也证实,miRNA-451通过直接靶向CAB39抑制PI3K/AKT信号通路,抑制胶质瘤细胞生长和增殖,诱导细胞凋亡。然而,具体的监管机制尚不清楚。哺乳动物雷帕霉素靶蛋白(mTOR)是多种细胞分化、增殖和迁移的中心调节因子。缺氧诱导因子(HIF)-1α参与肿瘤细胞的迁移和侵袭。据报道,VEGF过表达、肿瘤进展和不良临床结果之间存在密切关系。然而,miRNA-451是否通过调节mTOR、HIF-1α和VEGF的表达影响胶质瘤细胞的增殖和侵袭尚不清楚。本研究旨在通过探讨miRNA-451在体内和体外对胶质瘤细胞增殖和侵袭的影响,探讨其作用机制。相关的基因-蛋白相互作用也进行了预测和验证。miRNA-451可能通过靶向CAB39抑制mTOR/HIF-1α/VEGF通路,从而抑制胶质瘤细胞的增殖和侵袭。逆转录聚合酶链反应证实,用含有miRNA-451的慢病毒转染胶质瘤细胞可提高miR-451的表达水平。miR-451表达上调通过靶向CAB39,调控mTOR/HIF-1α/VEGF信号通路,在体外和体内抑制胶质瘤细胞的生长和侵袭。基于这些结果,miR-451通过靶向CAB39抑制mTOR/HIF-1α/VEGF信号通路,在体外和体内抑制胶质瘤细胞的增殖和侵袭。因此,miR-451可能成为胶质瘤治疗的新靶点。
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MiRNA-451 Inhibits Glioma Cell Proliferation and Invasion Through the mTOR/HIF-1α/VEGF Signaling Pathway by Targeting CAB39.

MicroRNAs (miRNAs) are widely expressed and regulate most biological functions. According to several research groups, miR-451 expression is decreased in glioma cells. A previous study also confirmed that miRNA-451 inhibits the PI3K/AKT signaling pathway by directly targeting CAB39, which inhibits glioma cell growth and proliferation and induces apoptosis. However, the specific regulatory mechanism is unclear. Mammalian target of rapamycin (mTOR) is a central regulator of the differentiation, proliferation, and migration of a variety of cells. Hypoxia-inducible factor (HIF)-1α is involved in tumor cell migration and invasion. Close relationships among VEGF overexpression, tumor progression, and poor clinical outcomes have been reported. However, whether miRNA-451 influences glioma cell proliferation and invasion by regulating mTOR, HIF-1α, and VEGF expression remains unknown. This study aimed to assess the effects of miRNA-451 on glioma cell proliferation and invasion in vivo and in vitro by investigating its mechanism. Related gene-protein interactions were also predicted and verified. By targeting CAB39, miRNA-451 likely represses the mTOR/HIF-1α/VEGF pathway to inhibit glioma cell proliferation and invasion. Reverse transcription polymerase chain reaction confirmed that transfection of glioma cells with a lentivirus containing miRNA-451 elevated the expression level of miR-451. Upregulation of miR-451 expression suppressed the growth and invasion of glioma cells in vitro and in vivo by targeting CAB39 and modulating the mTOR/HIF-1α/VEGF signaling pathway. Based on these results, miR-451 suppresses glioma cell proliferation and invasion in vitro and in vivo via suppression of the mTOR/HIF-1α/VEGF signaling pathway by targeting CAB39. Therefore, miR-451 may be a new target for glioma treatment.

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来源期刊
Human Gene Therapy Clinical Development
Human Gene Therapy Clinical Development CRITICAL CARE MEDICINEMEDICINE, RESEARCH &-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
7.20
自引率
0.00%
发文量
0
期刊介绍: Human Gene Therapy (HGT) is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes important advances in DNA, RNA, cell and immune therapies, validating the latest advances in research and new technologies.
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