Circular RNA Complement Factor H (CFH) Promotes Glioma Progression by Sponging miR-149 and Regulating AKT1.
Circular RNA Complement Factor H (CFH) Promotes Glioma Progression by Sponging miR-149 and Regulating AKT1.
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DOI：
10.12659/msm.910180
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发表时间：
2018-08-16
期刊：
影响因子：
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通讯作者：
Hui X
中科院分区：
文献类型：
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作者：
Bian A;Wang Y;Liu J;Wang X;Liu D;Jiang J;Ding L;Hui X
环状RNA（circRNA）在哺乳动物中广泛表达，可以调节人类肿瘤的发生和进展。 has_circ_0015758 (circ-CFH) 是来自 1 号染色体 GRCh37/hg19 片段的外显子 circRNA 转录物，与蛋白质编码基因补体因子 H (CFH) 同源。目前，circ-CFH在神经胶质瘤中的功能仍不清楚。在我们的研究中，通过 qRT-PCR 检测分析了 circ-CFH、miR-149 和 Akt1 mRNA 表达水平。为了研究circ-CFH在细胞增殖中的功能，利用circ-CFH siRNA建立了circ-CFH敲低模型。通过CCK-8和集落形成测定以及体内实验来测量细胞增殖能力。此外，通过荧光素酶报告基因测定评估了 circ-CFH 和 miR-149 之间的相互作用。 Circ-CFH 表达在神经胶质瘤组织中显着上调，并且与肿瘤分级相关。 U251 和 U373 神经胶质瘤细胞系中的 Circ-CFH 表达水平也显着较高。 Circ-CFH 敲低抑制细胞增殖和集落形成能力。荧光素酶测定表明，circ-CFH 作为 miR-149 海绵发挥作用，并抑制其在 U251 和 U373 细胞中的功能。随后，AKT1 被确定为 circ-CFH/miR-149 轴的直接靶标。 Circ-CFH 通过海绵 miR-149 和调节 AKT1 信号通路促进神经胶质瘤进展。 circ-CFH/miR-149/AKT1 调节轴可能是神经胶质瘤治疗的潜在靶点。
Circular RNAs (circRNAs) are widely expressed in mammals and can regulate the development and progression of human tumors. has_circ_0015758 (circ-CFH) is an exon circRNA transcript from the GRCh37/hg19 fragment of chromosome 1 and is homologous to the protein-coding gene complement factor H (CFH). Currently, the function of circ-CFH in glioma remains unclear. In our study, circ-CFH, miR-149, and Akt1 mRNA expression levels were analyzed by qRT-PCR assays. To investigate the function of circ-CFH in cell proliferation, circ-CFH knockdown models were established by using circ-CFH siRNAs. Cell proliferation abilities were measured by CCK-8 and colony formation assays and in vivo experiments. In addition, the interaction between circ-CFH and miR-149 was assessed by luciferase reporter assays. Circ-CFH expression was significantly upregulated in glioma tissue and was correlated with tumor grade. Circ-CFH expression levels were also markedly higher in U251 and U373 glioma cell lines. Circ-CFH knockdown inhibited cell proliferation and colony formation abilities. Luciferase assays indicated that circ-CFH functions as a miR-149 sponge and inhibits its function in U251 and U373 cells. Subsequently, AKT1 was identified as a direct target of the circ-CFH/miR-149 axis. Circ-CFH promotes glioma progression by sponging miR-149 and regulating the AKT1 signaling pathway. The circ-CFH/miR-149/AKT1 regulation axis may be a potential target for glioma therapy.