H19 Functions as a Competing Endogenous RNA to Regulate EMT by Sponging miR-130a-3p in Glioma
H19 Functions as a Competing Endogenous RNA to Regulate EMT by Sponging miR-130a-3p in Glioma
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H19 在神经胶质瘤中作为竞争性内源 RNA 通过海绵 miR-130a-3p 调节 EMT
DOI：
10.1159/000494002
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发表时间：
2018-01-01
影响因子：
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通讯作者：
You, Yongping
中科院分区：
文献类型：
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作者：
Hu, Qi;Yin, Jianxing;You, Yongping
背景/目的：胶质瘤是最具破坏性的肿瘤之一，预后差。长链非编码RNA（lncRNA）已成为包括胶质瘤在内的多种肿瘤的重要调控因子。一种经典的lncRNA-H19，发现其在人脑胶质瘤组织和细胞系中高度表达，并与肿瘤进展相关，从而预测胶质瘤患者的临床结局。然而，H19在胶质瘤中的整体生物学功能及其机制尚未完全了解。研究方法：首先，我们通过对5个测序数据集的分析，分析了不同级别胶质瘤组织中H19的改变，并进行qRT-PCR以证实结果。接下来，我们评估了H19对胶质瘤细胞迁移、侵袭和EMT过程的影响。采用荧光素酶法和RIP法分析H19和SOX 4的相关性。结果：H19在胶质瘤组织中呈高表达。H19的表达下调导致N-cadherin和Vimentin的表达减少，从而抑制了细胞的迁移、侵袭和EMT过程。H19和SOX 4都是miR-130 a-3 p的直接靶点。H19可以通过海绵状吸收miR-130 a-3 p与SOX 4竞争。结论：这些结果为H19作为一种癌基因在胶质瘤组织中的功能提供了可能，并为胶质瘤的治疗提供了一种新的策略。
Background/Aims: Glioma is one of the most devasting tumors and confers dismal prognosis. Long noncoding RNAs(lncRNAs) have emerged as important regulators in various tumors including glioma. A classic lncRNA-H19, which is found to be highly expressed in human glioma tissues and cell lines, and is associated with tumor progression thus predicating clinical outcomes in glioma patients. However, the overall biological functions and their mechanism of H19 in glioma are not fully understood. Methods: Firstly, we analyzed H19 alterations in different grades of glioma tissues through an analysis of 5 sequencing datasets and qRT-PCR was performed to confirm the results. Next, we evaluated the effect of H19 on glioma cells migration, invasion and EMT process. Luciferase assays and RIP assays were employed to figure out the correlation of H19 and SOX4. Results: H19 was overexpressed in glioma tissues. Down-regulation of H19 led to the inhibition of migration, invasion and EMT process with a reduction in N-cadherin and Vimentin. H19 and SOX4 are both direct target of miR-130a-3p. H19 could compete with SOX4 via sponging miR-130a-3p. Conclusion: Taken together, these results provide a possible function of H19 as an oncogene in glioma tissues and provide a potential new therapeutic strategy for human glioma.