Kotaki Ryutaro, Higuchi Hiroshi, Ogiya Daisuke, Katahira Yasuhiro, Kurosaki Natsumi, Yukihira Naoko, Ogata Jun, Yamamoto Haruna, Mohamad Alba Syakira, Azhim Azran, Kitajima Tatsuo, Inoue Shigeaki, Morishita Kazuhiro, Ono Koh, Koyama-Nasu Ryo, Kotani Ai
Division of Hematological Malignancy, Institute of Medical Sciences, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193, Japan.
Int J Hematol. 2017 Dec;106(6):811-819. doi: 10.1007/s12185-017-2314-1. Epub 2017 Aug 22.
miR-1 and miR-133 are clustered on the same chromosomal loci and are transcribed together as a single transcript that is positively regulated by ecotropic virus integration site-1 (EVI1). Previously, we described how miR-133 has anti-tumorigenic potential through repression of EVI1 expression. It has also been reported that miR-1 is oncogenic in the case of acute myeloid leukemia (AML). Here, we show that expression of miR-1 and miR-133, which have distinct functions, is differentially regulated between AML cell lines. Interestingly, the expression of miR-1 and EVI1, which binds to the promoter of the miR-1/miR-133 cluster, is correlative. The expression levels of TDP-43, an RNA-binding protein that has been reported to increase the expression, but inhibits the activity, of miR-1, were not correlated with expression levels of miR-1 in AML cells. Taken together, our observations raise the possibility that the balance of polycistronic miRNAs is regulated post-transcriptionally in a hierarchical manner possibly involving EVI1, suggesting that the deregulation of this balance may play some role in AML cells with high EVI1 expression.
miR-1和miR-133聚集在同一染色体位点上，并作为一个单一转录本一起转录，该转录本受嗜异性病毒整合位点1（EVI1）的正向调控。此前，我们描述了miR-133如何通过抑制EVI1表达而具有抗肿瘤发生的潜力。也有报道称，在急性髓系白血病（AML）中miR-1具有致癌性。在这里，我们表明，具有不同功能的miR-1和miR-133的表达在AML细胞系之间受到差异调控。有趣的是，与miR-1/miR-133簇启动子结合的miR-1和EVI1的表达是相关的。TDP-43是一种RNA结合蛋白，据报道它可增加miR-1的表达，但抑制其活性，其表达水平与AML细胞中miR-1的表达水平不相关。综上所述，我们的观察结果提出了一种可能性，即多顺反子miRNA的平衡可能在转录后以一种可能涉及EVI1的分层方式受到调控，这表明这种平衡的失调可能在EVI1高表达的AML细胞中起一定作用。
