MicroRNAs (miRNAs) are a class of endogenous, evolutionarily conserved small non-coding RNA molecules that mediate the posttranscriptional processing of target genes, 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 a recent study led by researchers from Shanghai Jiao Tong University School of Medicine, they found that down regulation of miR-598 was a frequent event in CRC tissues compared to the paracarcinoma tissues. Their study also demonstrated that miR-598 was implicated in CRC metastasis.

Transwell migration assay and miRNA microarray service revealed that elevated miR-598 expression reduces CRC cell migration. The study also showed that suppression of miR-598 expression induces CRC cell epithelialmesenchymal transition(EMT) and overexpression of miR-598 inhibits CRC cell EMT. In addition, target prediction identified JAG1 as a putative target of miR-598.

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miRNA-598 is downregulated in CRC tissues compared to the corresponding normal. (A) Cluster analysis of miRNAs expression of CRC tissues (T1-T4) and the corresponding normal tissues (N1-N4). (B) qRT-PCR analysis showed that miR-598 was downregulated in CRC tissues compared to the corresponding normal tissues.

Knockdown of miR-598 was shown to upregulate JAG1 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, while decreased Notch2 expression suppresses CRC cells metastasis and EMT.

Together, these results indicate that miR-598 is a novel regulator of colorectal cancer metastasis. These data suggest miR-598 is implicated in regulating Epithelial-mesenchymal transitions by directly suppressing its downstream target gene JAG1 to inactivate Notch signaling pathway.

 

Reference
J. Chen, H. Zhang, Y. Chen, G. Qiao, W. Jiang, P. Ni, X. Liu, L. Ma (2017) miR-598 inhibits metastasis in colorectal cancer by suppressing JAG1/Notch2 pathway stimulating EMT Exp. Cell Res. 352(1) 104-112 doi: 10.1016/j.yexcr.2017.01.022 [abstract]

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