Document Detail


MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2.
MedLine Citation:
PMID:  20548334     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Emerging evidence has shown the association of aberrantly expressed microRNAs (miRNAs) with tumor development and progression. However, little is known about the potential role of miRNAs in gastric carcinogenesis. Here, we performed miRNA microarray to screen miRNAs differentially expressed in the paired gastric cancer and their adjacent nontumor tissues and found that miR-375 was greatly downregulated in gastric cancer tissues. Quantitative real-time PCR analysis verified that miR-375 expression was significantly decreased in more than 90% of primary gastric cancers compared with their nontumor counterparts from patients undergoing gastric resection. Overexpression of miR-375 significantly inhibited gastric cancer cell proliferation in vitro and in vivo. Forced expression of miR-375 in gastric cancer cells significantly reduced the protein level of Janus kinase 2 (JAK2) and repressed the activity of a luciferase reporter carrying the 3'-untranslated region of JAK2, which was abolished by mutation of the predicted miR-375-binding site, indicating that JAK2 may be a miR-375 target gene. Either inhibition of JAK2 activity by AG490 or silencing of JAK2 by RNAi suppressed gastric cancer cell proliferation resembling that of miR-375 overexpression. Moreover, ectopic expression of JAK2 can partially reverse the inhibition of cell proliferation caused by miR-375. Finally, we found a significant inverse correlation between miR-375 expression and JAK2 protein level in gastric cancer. Thus, these data suggest that miR-375 may function as a tumor suppressor to regulate gastric cancer cell proliferation potentially by targeting the JAK2 oncogene, implicating a role of miR-375 in the pathogenesis of gastric cancer.
Authors:
Ling Ding; Yanjun Xu; Wei Zhang; Yujie Deng; Misi Si; Ying Du; Haomi Yao; Xuyan Liu; Yuehai Ke; Jianmin Si; Tianhua Zhou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-15
Journal Detail:
Title:  Cell research     Volume:  20     ISSN:  1748-7838     ISO Abbreviation:  Cell Res.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-02     Completed Date:  2010-10-04     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  9425763     Medline TA:  Cell Res     Country:  China    
Other Details:
Languages:  eng     Pagination:  784-93     Citation Subset:  IM    
Affiliation:
The Center for Diseases Modeling and Program in Molecular and Cell Biology, Zhejiang University School of Medicine, Hangzhou, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Proliferation / drug effects
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Humans
Janus Kinase 2 / antagonists & inhibitors*
Mice
MicroRNAs / genetics*,  physiology
Neoplasm Transplantation
Stomach Neoplasms / etiology,  genetics*
Transplantation, Heterologous
Chemical
Reg. No./Substance:
0/MIRN375 microRNA, human; 0/MicroRNAs; EC 2.7.10.1/Janus Kinase 2; EC 2.7.10.2/JAK2 protein, human

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