miR-24-3p and miR-27a-3p promote cell proliferation in glioma cells via cooperative regulation of MXI1
miR-24-3p and miR-27a-3p promote cell proliferation in glioma cells via cooperative regulation of MXI1
复制标题
miR-24-3p和miR-27a-3p通过协同调节MXI1促进胶质瘤细胞增殖
DOI：
10.3892/ijo.2012.1742
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发表时间：
2013-02-01
影响因子：
5.2
通讯作者：
Jiang, Songshan
中科院分区：
文献类型：
--
作者：
Xu, Weiyi;Liu, Mingfa;Jiang, Songshan
microRNA（miRNAs）是一类在转录后水平调控基因表达的小分子非编码RNA。miRNAs的异常表达经常发生在肿瘤中。虽然miR-24- 3 p和miR-27 a-3 p这两种miRNAs来自miR-23 a类似于27 a类似于24-2和miR-23 b类似于27 b类似于24-1的两个重复基因簇，这两个重复基因簇被发现在多种癌症中失调，但这两个簇的协同作用以及这两种miRNAs在肿瘤中的功能尚未完全表征。在此，我们使用MTT法显示过表达miR-24- 3 p和miR-27 a-3 p可以促进细胞增殖。通过综合生物信息学分析和实验证实，我们确定了MXI 1作为miR-24- 3 p和miR-27 a-3 p的直接靶点，MXI 1已被发现通过影响c-Myc作为肿瘤抑制基因。当通过miR-24- 3 p或miR-27 a-3 p靶向MXI 1 3'非翻译区时，荧光素酶活性减弱。这两种miRNAs通过靶向MXI 1促进胶质瘤细胞增殖，并通过拯救实验证实了该实验。此外，我们的研究结果表明，类似于27 a类似于24-2的两个miR-23 a簇和类似于27 b类似于24-1的miR-23 b簇协同调节MXI 1。这些发现首次揭示了来自两个簇的miR-24- 3 p和miR-27 a-3 p在通过MXI 1促进细胞增殖中的协同作用的新功能。此外，我们观察到miR-27 a-3 p在胶质瘤组织中上调。
MicroRNAs (miRNAs) are small, non-coding RNAs which regulate gene expression at the post-transcriptional level. Abnormal expression of miRNAs occurs frequently in tumors. Although the two miRNAs miR-24-3p and miR-27a-3p come from two duplicated gene clusters of miR-23a similar to 27a similar to 24-2 and miR-23b similar to 27b similar to 24-1 which are found to be deregulated in a variety of cancers, the role of cooperation of the two clusters and the function of the two miRNAs in tumors have not been completely characterized. Here, we show that overexpression of miR-24-3p and miR-27a-3p could promote cell proliferation using the MTT assay. By integrated bioinformatic analysis and experimental confirmation, we identified MXI1, which has been found to act as a tumor suppressor gene by affecting c-Myc, as a direct target of miR-24-3p and miR-27a-3p. While targeting the MXI1 3' untranslated region by miR-24-3p or miR-27a-3p, luciferase activity was attenuated. The two miRNAs promote glioma cell proliferation via targeting MXI1 and the experiment was confirmed by the rescue experiments. Furthermore, our results show that two clusters of miR-23a similar to 27a similar to 24-2 and miR-23b similar to 27b similar to 24-1 regulate MXI1 synergistically. These findings reveal, for the first time, the novel functions of cooperation of miR-24-3p and miR-27a-3p from two clusters in promoting cell proliferation through MXI1. Additionally, we observed that miR-27a-3p is upregulated in glioma tissues.