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Hsa_circ_0043278 通过海绵吸附 miR-638 作为竞争性内源性 RNA 促进多形性胶质母细胞瘤的进展。

Hsa_circ_0043278 functions as competitive endogenous RNA to enhance glioblastoma multiforme progression by sponging miR-638.

机构信息

Department of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou 730000, China.

Department of Surgical Oncology, The First hospital of Lanzhou University, Lanzhou 730000, China.

出版信息

Aging (Albany NY). 2020 Nov 5;12(21):21114-21128. doi: 10.18632/aging.103603.

Abstract

Circular RNAs have a critical function in the pathogenesis of many diseases and can function as competing endogenous RNA or miRNA sponges to inhibit miRNA and therefore upregulate the expression of target genes. However, little is known about the role of has_circRNA_0043278 (circ_0043278) in glioblastoma multiforme (GBM) and its potential downstream miRNA targets. This work validated that circ_0043278 is highly expressed in GMB cell lines and tissues, while knockdown circ_0043278 inhibited GBM cell migration, proliferation, and invasion and tumorigenesis . Dual-luciferase reporter assay determined that circ_0043278 directly sponged miR-638 to upregulate the expression of HOXA9, which can activate downstream Wnt/β-catenin signaling in GBM. Moreover, miR-638 inhibition reversed circ_0043278 silencing-induced impairment of malignant tumor behavior. These results showed that circ-0043278/miRNA-638/ Homeobox A9 (HOXA9) axis had a vital function in promoting GBM progression. Our findings may provide potential new targets for the diagnosis and therapy of GBM.

摘要

环状 RNA 在许多疾病的发病机制中具有关键作用,可作为竞争性内源性 RNA 或 miRNA 海绵,抑制 miRNA,从而上调靶基因的表达。然而,环状 RNA_0043278(circ_0043278) 在多形性胶质母细胞瘤(GBM)中的作用及其潜在的下游 miRNA 靶基因知之甚少。本研究验证了 circ_0043278 在 GBM 细胞系和组织中高表达,而敲低 circ_0043278 抑制了 GBM 细胞的迁移、增殖和侵袭以及肿瘤发生。双荧光素酶报告基因检测确定 circ_0043278 可直接与 miR-638 结合,上调 HOXA9 的表达,从而激活 GBM 中 Wnt/β-catenin 信号通路。此外,miR-638 抑制逆转了 circ_0043278 沉默诱导的恶性肿瘤行为损伤。这些结果表明 circ-0043278/miRNA-638/同源盒 A9(HOXA9) 轴在促进 GBM 进展中具有重要作用。我们的研究结果可能为 GBM 的诊断和治疗提供新的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a83/7695414/284f45623323/aging-12-103603-g001.jpg

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