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长链非编码 RNA AGAP2-AS1 通过海绵吸附 miR-15a/b-5p 来上调 HDGF 的表达,从而激活 Wnt/β-catenin 信号通路,促进神经胶质瘤细胞的增殖。

Long non-coding RNA AGAP2-AS1 promotes the proliferation of glioma cells by sponging miR-15a/b-5p to upregulate the expression of HDGF and activating Wnt/β-catenin signaling pathway.

机构信息

Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, Yiyuan Street, Nangang District, Harbin, Heilongjiang, China.

Department of Neurology, Shanghai Tongren Hospital, No. 1111, Xianxia Road, Changning District, Shanghai, China.

出版信息

Int J Biol Macromol. 2019 May 1;128:521-530. doi: 10.1016/j.ijbiomac.2019.01.121. Epub 2019 Jan 23.

Abstract

Glioma is a kind of malignant brain tumor which damages the central nervous system of adults. Recent years, the molecular mechanism involved in the initiation and progression of glioma has been widely reported. Long non-coding RNAs (lncRNAs) have been proved to be significant modulators in the biological processes of glioma. In this study, we found that lncRNA AGAP2-AS1 was differentially expressed in glioma tissue samples and cell lines. Kaplan-Meier method was used to analyze the correlation between AGAP2-AS1 expression and the overall survival of glioma patients. Higher expression of AGAP2-AS1 was correlated with the lower overall survival of glioma patients. Functionally, AGAP2-AS1 knockdown inhibited glioma cell proliferation and accelerated glioma cell apoptosis. Mechanistically, AGAP2-AS1 upregulated HDGF by sponging miR-15a/b-5p. The function of AGAP2-AS1-miR-15a/b-5p-HDGF axis was confirmed by performing rescue assays. Experimental results suggested that miR-15a/b-5p and HDGF involved in AGAP2-AS1-mediated glioma cell proliferation. Moreover, AGAP2-AS1 and HDGF were found to activate Wnt/β-catenin signaling pathway in glioma cell lines. In summary, this study demonstrated that AGAP2-AS1 promoted glioma cell proliferation by sponging miR-15a/b-5p to upregulate the expression of HDGF.

摘要

神经胶质瘤是一种恶性脑肿瘤,会损害成年人的中枢神经系统。近年来,涉及神经胶质瘤发生和进展的分子机制已被广泛报道。长链非编码 RNA(lncRNA)已被证明是神经胶质瘤生物学过程中的重要调节剂。在这项研究中,我们发现 lncRNA AGAP2-AS1 在神经胶质瘤组织样本和细胞系中表达差异。Kaplan-Meier 法分析 AGAP2-AS1 表达与神经胶质瘤患者总生存期的相关性。AGAP2-AS1 高表达与神经胶质瘤患者总生存期降低相关。功能上,AGAP2-AS1 敲低抑制神经胶质瘤细胞增殖并加速神经胶质瘤细胞凋亡。机制上,AGAP2-AS1 通过海绵吸附 miR-15a/b-5p 而上调 HDGF。通过进行挽救实验证实了 AGAP2-AS1-miR-15a/b-5p-HDGF 轴的功能。实验结果表明,miR-15a/b-5p 和 HDGF 参与了 AGAP2-AS1 介导的神经胶质瘤细胞增殖。此外,还发现 AGAP2-AS1 和 HDGF 在神经胶质瘤细胞系中激活了 Wnt/β-catenin 信号通路。总之,本研究表明,AGAP2-AS1 通过海绵吸附 miR-15a/b-5p 上调 HDGF 的表达促进神经胶质瘤细胞增殖。

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