AntagomiR-27a Targets FOXO3a in Glioblastoma and Suppresses U87 Cell Growth in Vitro and in Vivo
AntagomiR-27a Targets FOXO3a in Glioblastoma and Suppresses U87 Cell Growth in Vitro and in Vivo
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DOI：
10.7314/apjcp.2013.14.2.963
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发表时间：
2013-01-01
影响因子：
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通讯作者：
Shao, Jun-Fei
中科院分区：
文献类型：
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作者：
Ge, Yun-Fei;Sun, Jun;Shao, Jun-Fei
目的：研究AnagomiR-27A抑制剂对胶质母细胞瘤细胞的作用。方法：采用定量逆转录聚合酶链式反应(qRT-PCR)检测miR-27A在人脑胶质母细胞瘤标本和脑外伤减压手术切除的正常脑组织中的表达水平，通过生物信息学数据库筛选miR-27A的预测靶基因，并用基因报告分析方法进行验证，通过四甲基偶氮唑盐比色法和5-乙炔基-2‘-脱氧尿苷(EDU)标记分析抗肿瘤基因对胶质瘤细胞侵袭和增殖的影响。建立BALB-c裸鼠胶质母细胞瘤裸鼠移植瘤模型，观察抗肿瘤药物R-27A对肿瘤生长的影响。结果：定量RT-PCR结果显示，与正常脑组织相比，胶质母细胞瘤组织中miR-27A的表达显著增加。TH miR-27A抑制剂显著抑制胶质母细胞瘤细胞的侵袭和增殖。Western blotting和报告分析证实FOXO3a是miR-27A的新靶点。体内肿瘤生长受到miR-27A抑制剂的抑制。结论：miR-27A可能在人脑胶质母细胞瘤中表达上调，而antagomiR-27A可抑制胶质母细胞瘤细胞的增殖和侵袭能力。
Objective: To study the effect of the antagomiR-27a inhibitor on glioblastoma cells. Methods: The miR-27a expression level in specimens of human glioblastoma and normal human brain tissues excised during decompression for traumatic brain injury was assessed using qRT-PCR; The predicted target gene of miR-27a was screened out through bioinformatics databases, and the predicted gene was verified using genetic report assays; the effect of antagomiR-27a on the invasion and proliferation of glioma cells was analyzed using MTT assays and 5-ethynyl-2'-deoxyuridine (EdU) labeling. A xenograft glioblastoma model in BALB-c nude mice was established to detect the effect of antagomiR-27a on tumour growth. Results: qRT-PCR results showed that miR-27a significantly increased in specimens from glioblastoma comparing with normal human brain tissues. Th miR-27a inhibitor significantly suppressed invasion and proliferation of glioblastoma cells. FOXO3a was verified as a new target of miR-27a by Western blotting and reporter analyzes. Tumor growth in vivo was suppressed by administration of the miR-27a inhibitor. Conclusion: MiR-27a may be up-regulated in human glioblastoma, and antagomiR-27a could inhibit the proliferation and invasion ability of glioblastoma cells.