Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.
PLoS One. 2011 Jan 14;6(1):e16264. doi: 10.1371/journal.pone.0016264.
MicroRNAs (miRNAs) are short, non-coding RNAs that regulate the expression of multiple target genes. Deregulation of miRNAs is common in human tumorigenesis. Low level expression of miR-26b has been found in glioma cells. However, its underlying mechanism of action has not been determined.
METHODOLOGY/PRINCIPAL FINDINGS: Real-time PCR was employed to measure the expression level of miR-26b in glioma patients and cells. The level of miR-26b was inversely correlated with the grade of glioma. Ectopic expression of miR-26b inhibited the proliferation, migration and invasion of human glioma cells. A binding site for miR-26b was identified in the 3'UTR of EphA2. Over-expression of miR-26b in glioma cells repressed the endogenous level of EphA2 protein. Vasculogenic mimicry (VM) experiments were performed to further confirm the effects of miR-26b on the regulation of EphA2, and the results showed that miR-26b inhibited the VM processes which regulated by EphA2.
This study demonstrated that miR-26b may act as a tumor suppressor in glioma and it directly regulates EphA2 expression. EphA2 is a direct target of miR-26b, and the down-regulation of EphA2 mediated by miR-26b is dependent on the binding of miR-26b to a specific response element of microRNA in the 3'UTR region of EphA2 mRNA.
微小 RNA（miRNAs）是一种短的非编码 RNA，可调节多个靶基因的表达。miRNAs 的失调在人类肿瘤发生中很常见。在神经胶质瘤细胞中发现 miR-26b 的表达水平较低。然而，其作用的潜在机制尚未确定。
方法/主要发现：实时 PCR 用于测量神经胶质瘤患者和细胞中 miR-26b 的表达水平。miR-26b 的水平与神经胶质瘤的分级呈负相关。miR-26b 的异位表达抑制了人神经胶质瘤细胞的增殖、迁移和侵袭。在 EphA2 的 3'UTR 中鉴定到 miR-26b 的结合位点。miR-26b 在神经胶质瘤细胞中的过表达抑制 EphA2 蛋白的内源性水平。进行血管生成拟态（VM）实验以进一步证实 miR-26b 对 EphA2 调节的影响，结果表明 miR-26b 抑制 EphA2 调节的 VM 过程。
本研究表明 miR-26b 可能在神经胶质瘤中作为肿瘤抑制因子发挥作用，并且直接调节 EphA2 的表达。EphA2 是 miR-26b 的直接靶标，miR-26b 通过 EphA2 mRNA 的 3'UTR 区中的 miR-26b 与特定的微 RNA 反应元件的结合来调节 EphA2 的下调。
