miR-598 inhibits metastasis in colorectal cancer by suppressing JAG1/Notch2 pathway stimulating EMT.
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 JAG1 as a putative target of miR-598. 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. 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 JAG1 to inactivate Notch signaling pathway.
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Jia
J
Chen
Department of Laboratory, Shanghai Xuhui Central Hospital, Shanghai 200031, China.
Haichen
H
Zhang
Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
Ying
Y
Chen
Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
Guanglei
G
Qiao
Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
Weihua
W
Jiang
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: nipeihua@126.com.
Peihua
P
Ni
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: liuxiangfan1976@163.com.
Xiangfan
X
Liu
Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China. Electronic address: researcharticle@163.com.
Lijun
L
Ma
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D058750:Epithelial-Mesenchymal Transition; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000072100:Jagged-1 Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051883:Receptor, Notch2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; C000619454:MIRN-598 microRNA, human; D035683:MicroRNAs; C497764:NOTCH2 protein, human; D012333:RNA, Messenger; D051883:Receptor, Notch2
Colorectal cancer (CRC); Epithelial-mesenchymal transition (EMT); JAG1; Metastasis; miR-598