Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China (mainland).
Med Sci Monit. 2018 Aug 16;24:5704-5712. doi: 10.12659/MSM.910180.
BACKGROUND 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. MATERIAL AND METHODS 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. RESULTS 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. CONCLUSIONS 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.
环状 RNA(circRNAs)广泛存在于哺乳动物中,可调节人类肿瘤的发生和发展。has_circ_0015758(circ-CFH)是染色体 1 的 GRCh37/hg19 片段上的一个外显子 circRNA 转录本,与蛋白编码基因补体因子 H(CFH)同源。目前,circ-CFH 在神经胶质瘤中的功能尚不清楚。
在本研究中,通过 qRT-PCR 分析检测 circ-CFH、miR-149 和 Akt1 mRNA 的表达水平。通过使用 circ-CFH siRNAs 建立 circ-CFH 敲低模型来研究 circ-CFH 在细胞增殖中的功能。通过 CCK-8 和集落形成实验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实验评估 circ-CFH 与 miR-149 之间的相互作用。
circ-CFH 在神经胶质瘤组织中表达显著上调,与肿瘤分级相关。circ-CFH 在 U251 和 U373 神经胶质瘤细胞系中的表达水平也明显更高。circ-CFH 敲低抑制细胞增殖和集落形成能力。荧光素酶实验表明 circ-CFH 作为 miR-149 的海绵体,抑制其在 U251 和 U373 细胞中的功能。随后,AKT1 被鉴定为 circ-CFH/miR-149 轴的直接靶标。
circ-CFH 通过海绵吸附 miR-149 并调节 AKT1 信号通路促进神经胶质瘤的进展。circ-CFH/miR-149/AKT1 调控轴可能是神经胶质瘤治疗的潜在靶点。