Overexpression of MicroRNA-216a Suppresses Proliferation, Migration, and Invasion of Glioma Cells by Targeting Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 5.

Overexpression of MicroRNA-216a Suppresses Proliferation, Migration, and Invasion of Glioma Cells by Targeting Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 5.
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MicroRNA-216a 的过表达通过靶向富含亮氨酸重复序列的 G 蛋白偶联受体 5 来抑制胶质瘤细胞的增殖、迁移和侵袭

DOI:
10.3727/096504017x14874323871217
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发表时间:
2017-09-21
期刊:
影响因子:
3.1
通讯作者:
Tian Y
Tian Y
中科院分区:
医学2区
文献类型:
--
作者:
Zhang J;Xu K;Shi L;Zhang L;Zhao Z;Xu H;Liang F;Li H;Zhao Y;Xu X;Tian Y

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越来越多的研究表明microRNAs(miRNAs)参与了胶质瘤的发生发展。MicroRNA-216 a在许多类型的癌症中被报道为肿瘤相关的miRNA,无论是作为癌基因还是作为肿瘤抑制基因。然而,关于miR-216 a在胶质瘤中的功能知之甚少。本研究旨在探讨miR-216 a在胶质瘤中的潜在作用。我们发现miR-216 a在胶质瘤组织和细胞系中显著降低。miR-216 a的过表达显着抑制胶质瘤细胞的增殖、迁移和侵袭。通过生物信息学分析、双荧光素酶报告基因分析、实时定量聚合酶链反应和Western blot分析,确定富含亮氨酸重复序列的G蛋白偶联受体5(LGR 5)为胶质瘤细胞中miR-216 a的靶基因。此外,miR-216 a过表达抑制Wnt/β-catenin信号通路。LGR 5表达的恢复显著逆转了miR-216 a在胶质瘤细胞中的抗肿瘤作用。总之,这些发现表明miR-216 a在胶质瘤中具有肿瘤抑制作用,其通过靶向LGR 5抑制胶质瘤细胞增殖、迁移和侵袭。我们的研究表明,miR-216 a可能作为未来胶质瘤治疗的潜在治疗靶点。
Increasing studies have suggested that microRNAs (miRNAs) are involved in the development of gliomas. MicroRNA-216a has been reported to be a tumor-associated miRNA in many types of cancer, either as an oncogene or as a tumor suppressor. However, little is known about the function of miR-216a in gliomas. The present study was designed to explore the potential role of miR-216a in gliomas. We found that miR-216a was significantly decreased in glioma tissues and cell lines. Overexpression of miR-216a significantly suppressed the proliferation, migration, and invasion of glioma cells. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) was identified as a target gene of miR-216a in glioma cells by bioinformatics analysis, dual-luciferase reporter assay, real-time quantitative polymerase chain reaction, and Western blot analysis. Moreover, miR-216a overexpression inhibited the Wnt/β-catenin signaling pathway. The restoration of LGR5 expression markedly reversed the antitumor effect of miR-216a in glioma cells. Taken together, these findings suggest a tumor suppressor role for miR-216a in gliomas, which inhibits glioma cell proliferation, migration, and invasion by targeting LGR5. Our study suggests that miR-216a may serve as a potential therapeutic target for future glioma treatment.