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微小RNA-760通过调节基质金属蛋白酶2(MMP2)的表达,在胶质瘤的增殖、迁移和侵袭过程中发挥关键的调节作用。

MiR-760 exerts a critical regulatory role in glioma proliferation, migration, and invasion by modulating MMP2 expression.

作者信息

Qian Zhengting, Xin Heng, Jia Zhen, Xia Jiageng, Tang Yong, Li Xiang, Wu Heming, Fan Youwu

机构信息

Nanjing Medical University, 210000, Nanjing, JiangSu, China.

Department of Neurosurgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China.

出版信息

J Cancer. 2024 Apr 8;15(10):3076-3084. doi: 10.7150/jca.92518. eCollection 2024.

Abstract

Glioma represents the predominant subtype of brain tumor, characterized by an unfavorable prognosis. Current evidence indicates the involvement of microRNAs (miRNAs) in the initiation and progression of glioma malignancies. While miR-760 has been recognized in the context of tumorigenesis, its precise role in gliomas remains insufficiently explored. In this investigation, we harnessed the GSE25631 database to scrutinize the aberrant expression profiles of microRNAs, whereby the diminished expression of miR-760 in glioblastoma was validated. Our aim was to delineate the expression patterns of microRNA-760 (miR-760) and probe its prognostic significance within the realm of glioma. Employing quantitative real-time polymerase chain reaction, we ascertained the relative expression levels of miR-760 and MMP2 in glioma cell lines. The impact of miR-760 on cell proliferation, migration, and invasion was assessed through Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and Transwell assays. Bioinformatics analysis corroborated the downstream target gene of miR-760. Furthermore, a luciferase reporter experiment was conducted to pinpoint MMP2 as the direct target gene of miR-760. The assessment of MMP2 protein levels was accomplished through Western blotting and immunofluorescence techniques. Our data unequivocally revealed a substantial reduction in miR-760 expression within glioma tissues and cell lines. Heightened miR-760 levels exerted a restraining influence on the proliferation, migration, and invasion capabilities of glioma cell lines. The outcomes of our bioinformatics analysis unveiled the ability of miR-760 to engage with and curtail MMP2 expression. Collectively, these findings posit that miR-760 exerts a restraining influence on glioma growth by orchestrating the upregulation of miR-760 along the miR-760/MMP2 axis. The delineation of the miR-760/MMP2 axis promises to broaden our comprehension of the intricate molecular mechanisms underpinning glioma proliferation and may unveil prospective therapeutic avenues for the management of glioma.

摘要

胶质瘤是脑肿瘤的主要亚型,预后不良。目前的证据表明,微小RNA(miRNA)参与了胶质瘤恶性肿瘤的发生和发展。虽然miR-760在肿瘤发生的背景下已被认识,但其在胶质瘤中的确切作用仍未得到充分探索。在本研究中,我们利用GSE25631数据库来仔细研究微小RNA的异常表达谱,从而验证了胶质母细胞瘤中miR-760表达的降低。我们的目的是描绘微小RNA-760(miR-760)的表达模式,并探究其在胶质瘤领域的预后意义。采用定量实时聚合酶链反应,我们确定了miR-760和MMP2在胶质瘤细胞系中的相对表达水平。通过细胞计数试剂盒-8(CCK-8)、5-乙炔基-2'-脱氧尿苷(EdU)和Transwell实验评估了miR-760对细胞增殖、迁移和侵袭的影响。生物信息学分析证实了miR-760的下游靶基因。此外,进行了荧光素酶报告基因实验以确定MMP2是miR-760的直接靶基因。通过蛋白质印迹和免疫荧光技术完成了对MMP2蛋白水平的评估。我们的数据明确显示,胶质瘤组织和细胞系中miR-760的表达大幅降低。miR-760水平的升高对胶质瘤细胞系的增殖、迁移和侵袭能力产生了抑制作用。我们生物信息学分析的结果揭示了miR-760与MMP2表达结合并抑制其表达的能力。总的来说,这些发现表明,miR-760通过协调miR-760/MMP2轴的上调对胶质瘤生长产生抑制作用。miR-760/MMP2轴的描绘有望拓宽我们对胶质瘤增殖复杂分子机制的理解,并可能揭示胶质瘤治疗的潜在途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98f4/11064272/104d5fd7e46a/jcav15p3076g001.jpg

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