Document Detail

miR-124 inhibits cell proliferation in gastric cancer through down-regulation of SPHK1.
MedLine Citation:
PMID:  22450659     Owner:  NLM     Status:  MEDLINE    
SPHK1 expression is elevated in gastric cancer and is associated with shorter survival times for patients. However, the molecular mechanism of SPHK1 up-regulation in gastric cancer remains unclear. In the present study, we report that miR-124 down-regulated SPHK1 expression by directly targeting its 3'-untranslated region (3'-UTR) and that miR-124 expression was inversely correlated with SPHK1 expression in gastric cancer samples. Furthermore, we demonstrated that, similar to the effect of silencing SPHK1, up-regulation of miR-124 markedly inhibited proliferation and tumourigenicity of gastric cancer cells both in vitro and in vivo. This was found to be mechanistically associated with induction of cyclin-dependent kinase inhibitors p21$^{{\rm Cip1}}$ and p27$^{{\rm Kip1}}$, enhancement of the transcriptional activity of FOXO1 and suppression of AKT activity. Moreover, we showed that the re-introduction of SPHK1 (without the 3'-UTR), but not with the 3'-UTR, could abrogate the miR-124-mediated induction of p21$^{{\rm Cip1}}$ and p27$^{{\rm Kip1}}$, as well as rescue the miR-124-induced proliferation inhibition. Together, these results suggest that miR-124 has an important role in the suppression of gastric cancer and presents a novel mechanism of miRNA-mediated SPHK1 expression in cancer cells.
Jintang Xia; Zhiqiang Wu; Chunping Yu; Weiling He; Haiqing Zheng; Yulong He; Weihua Jian; Lianzhou Chen; Luanjing Zhang; Wen Li
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-23
Journal Detail:
Title:  The Journal of pathology     Volume:  227     ISSN:  1096-9896     ISO Abbreviation:  J. Pathol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-10     Completed Date:  2012-09-25     Revised Date:  2012-09-28    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  470-80     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Laboratory of Department of Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
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MeSH Terms
Adenocarcinoma / pathology*,  physiopathology
Cell Cycle / physiology
Cell Line, Tumor
Cell Proliferation*
Cell Transformation, Neoplastic
Cyclin-Dependent Kinase Inhibitor p21 / physiology
Cyclin-Dependent Kinase Inhibitor p27 / physiology
Down-Regulation / physiology*
Forkhead Transcription Factors / physiology
MicroRNAs / physiology*
Phosphotransferases (Alcohol Group Acceptor) / physiology*
Proto-Oncogene Proteins c-akt / physiology
Signal Transduction / physiology
Stomach Neoplasms / pathology*,  physiopathology
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p21; 0/FOXO1 protein, human; 0/Forkhead Transcription Factors; 0/MIRN124 microRNA, human; 0/MicroRNAs; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.-/sphingosine kinase; EC Proteins c-akt

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