miR-22 regulates expression of oncogenic neuro-epithelial transforming gene 1, NET1
miR-22 regulates expression of oncogenic neuro-epithelial transforming gene 1, NET1
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DOI：
10.1111/febs.12926
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发表时间：
2014-09-01
期刊：
影响因子：
5.4
通讯作者：
Bhattacharya, Alok
中科院分区：
文献类型：
--
作者：
Ahmad, Hafiz M.;Muiwo, Pamchui;Bhattacharya, Alok
microRNA通过调节其靶基因的表达来控制细胞过程。在这里，我们报告，神经上皮转化基因1（NET 1）是肿瘤抑制microRNA 22（miR-22）的目标。miR-22在来源于慢性髓性白血病（CML）患者的外周血单核细胞和CML细胞系K562中下调。NET 1被鉴定为miR-22的靶点之一，使用体外和体内实验。NET 1 30-UTR中位于miR-22结合位点的突变或天然存在的单核苷酸多态性被发现影响miR-22与NET 1 mRNA的结合。NET 1在K562细胞中的过表达导致增殖增加。然而，无论是过表达miR-22还是敲低NET 1表达，均观察到细胞增殖下降和细胞周期改变。我们还发现，miR-22或NET 1敲低的过表达抑制肌动蛋白纤维的形成，可能是通过下调NET 1，因为NET 1敲低也导致肌动蛋白纤维形成的耗尽。我们认为CML细胞的致癌特性可能是由于miR-22的表达改变导致NET 1的表达失调。
MicroRNAs control cellular processes by regulating expression of their target genes. Here we report that neuro-epithelial transforming gene 1 (NET1) is a target of tumor suppressor microRNA 22 (miR-22). miR-22 is downregulated in peripheral blood mononuclear cells derived from chronic myeloid leukemia (CML) patients and in CML cell line K562. NET1 was identified as one of the targets of miR-22 using both in vitro and in vivo experiments. Either mutations or naturally occurring single-nucleotide polymorphisms in NET1 30-UTR that map at the miR-22 binding site were found to affect binding of miR-22 to NET1 mRNA. Over expression of NET1 in K562 cells resulted in increased proliferation. However decreased proliferation and alteration in cell cycle were observed on either overexpression of miR-22 or knockdown of NET1 expression respectively. We also found that overexpression of miR-22 or NET1 knockdown inhibits actin fiber formation, probably by downregulation of NET1 as NET1 knockdown also resulted in depletion of actin fiber formation. We suggest that the oncogenic properties of CML cells are probably due to deregulated expression of NET1 as a result of altered expression of miR-22.