miR-598 inhibits metastasis in colorectal cancer by suppressing JAG1/Notch2 pathway stimulating EMT
miR-598 inhibits metastasis in colorectal cancer by suppressing JAG1/Notch2 pathway stimulating EMT
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miR-598通过抑制JAG1/Notch2通路刺激EMT来抑制结直肠癌转移
DOI：
10.1016/j.yexcr.2017.01.022
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发表时间：
2017-03-01
影响因子：
3.7
通讯作者：
Ma, Lijun
中科院分区：
文献类型：
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作者：
Chen, Jia;Zhange, Haichen;Ma, Lijun
microRNA（miRNAs）是一类内源性、进化上保守的非编码小RNA分子，介导靶基因的转录后过程，导致靶mRNA的翻译抑制或降解。一系列研究表明，miRNAs在肿瘤的发生、发展和进展中起着重要作用。在这项研究中，我们发现，与癌旁组织相比，miR-598的下调在CRC组织中是一个常见的事件。研究表明miR-598与结直肠癌转移有关。Transwell迁移试验显示，miR-598表达升高可降低CRC细胞迁移。此外，我们的研究表明，抑制miR-598表达可诱导CRC细胞上皮间质转化（EMT），过表达miR-598可抑制CRC细胞EMT。此外，生物信息学靶标预测鉴定了JAG！作为miR-598的假定靶点。miR-598的敲低显示上调JAG！表情此外，miR-598的过表达抑制了JAG 1的表达。当在CRC组织中进一步指定miR-598对JAG 1表达的调节时，也获得了一致的结果。此外，JAG 1的过表达诱导上皮间质转化（EMT）并促进CRC细胞的转移。Notch 2表达降低抑制CRC细胞转移和EMT。总之，这些结果表明miR-598是结直肠癌转移的新调节因子。我们的数据表明，miR-598通过直接抑制其下游靶基因JAG！阻断Notch信号通路。
MicroRNAs (miRNAs) are a class of endogenous, evolutionarily conserved small non -coding RNA molecules that mediate the posttranscriptional process of target gene, leading to translational repression or degradation of target mRNAs. A series of studies have indicated that miRNAs play an important role in tumor initiation, development and progression. In this study, we found that down regulation of miR-598 was a frequent event in CRC tissues compared to the paracarcinoma tissues. And the study demonstrated that miR-598 was implicated in CRC metastasis. Transwell migration assay revealed that elevated miR-598 expression reduces CRC cell migration. Moreover, our study showed that suppression of miR-598 expression induces CRC cell epithelialmesenchymal transition(EMT) and overexpression of miR-598 inhibits CRC cell EMT. In addition, bioinformatics target prediction identified JAG! as a putative target of miR-598. Knockdown of miR-598 was shown to upregulate JAG! expression. Furthermore, overexpression of miR-598 suppressed the expression of JAG1. Consistent results were also obtained when the regulation of JAG1 expression by miR-598 was further specified in CRC tissues. Moreover, overexpression of JAG1 induces epithelialmesenchymal transition(EMT) and promotes the metastasis of CRC cells. Decreased Notch2 expression suppresses CRC cells metastasis and EMT. Together, these results indicate that miR-598 is a novel regulator of colorectal cancer metastasis. Our data suggest miR-598 is implicated in regulating Epithelial-mesenchymal transitions by directly suppressing its downstream target gene JAG! to inactivate Notch signaling pathway.