State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China ; Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, China ; Department of Pathology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Neurosurgery Department, Epilepsy Centre, Guangzhou General Hospital, Guangzhou Command, PLA, Guangzhou, China ; HuaBo Bio-Pharmaceutic Institute of Guangzhou, Guangzhou, China.
PLoS One. 2013 Dec 23;8(12):e83055. doi: 10.1371/journal.pone.0083055. eCollection 2013.
Gliomas are the most common and aggressive primary tumors in the central nervous system. Recently, Max interactor-1 (MXI1), an antagonist of c-Myc that is involved in brain tumor progression, has been reported to be deregulated in a variety of tumors including glioma. However, the mechanism of MXI1 deregulation in gliomas remains unclear. In this study, we show that the relative expression level of MXI1 is markedly down-regulated in glioma cell lines. Using integrated bioinformatic analysis and experimental confirmation, we identified several miRNAs by screening a panel of predicted miRNAs that may regulate the MXI1 3'UTR. The strongest inhibitory miRNA, miR-155, can attenuate the activity of a luciferase reporter gene that is fused with the MXI1 3'UTR and decrease the expression levels of MXI1 mRNA and protein in U87 glioma cells. The potential role of miR-155 in promoting glioma cell proliferation by targeting MXI1 was confirmed in various glioma cell lines by rescue experiments using MTT assays, EdU incorporation assay, and cell counting experiments. In addition, we determined that the level of MXI1 mRNA was inversely correlated with the expression of miR-155 in 18 sets of glioblastoma multiforme specimens. These findings reveal for the first time that the targeting of MXI1 by miR-155 may result in a reduction in MXI1 expression and promote glioma cell proliferation; this result suggests a novel function of miR-155 in targeting MXI1 in glioma-genesis.
神经胶质瘤是中枢神经系统中最常见和侵袭性最强的原发性肿瘤。最近，Max 相互作用因子-1（MXI1）被报道在多种肿瘤中失调，包括神经胶质瘤，它是 c-Myc 的拮抗剂，参与脑肿瘤的进展。然而，MXI1 在神经胶质瘤中失调的机制尚不清楚。在这项研究中，我们表明 MXI1 的相对表达水平在神经胶质瘤细胞系中明显下调。通过筛选一组预测的 miRNA，我们进行了综合的生物信息学分析和实验验证，鉴定出了几个可能调节 MXI1 3'UTR 的 miRNA。最强的抑制性 miRNA，miR-155，可以减弱与 MXI1 3'UTR 融合的荧光素酶报告基因的活性，并降低 U87 神经胶质瘤细胞中 MXI1 mRNA 和蛋白的表达水平。通过 MTT 测定、EdU 掺入测定和细胞计数实验等挽救实验，在各种神经胶质瘤细胞系中证实了 miR-155 通过靶向 MXI1 促进神经胶质瘤细胞增殖的潜在作用。此外，我们确定了 18 组多形性胶质母细胞瘤标本中 MXI1 mRNA 的水平与 miR-155 的表达呈负相关。这些发现首次揭示了 miR-155 通过靶向 MXI1 可能导致 MXI1 表达减少并促进神经胶质瘤细胞增殖；这一结果表明 miR-155 在神经胶质瘤发生中靶向 MXI1 具有新的功能。
