In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 6 ( 2010-03-15), p. 2339-2349
Abstract:
We investigated expression profiles of microRNA (miRNA) in gastric carcinomas by use of a miRNA microarray platform covering a total of 470 human miRNAs. We identified 39 differentially expressed miRNAs in gastric carcinoma, of which six were significantly downregulated and the other 33 were upregulated. We found that miRNA-375 (miR-375) was the most downregulated and that its ectopic expression in gastric carcinoma cells markedly reduced cell viability via the caspase-mediated apoptosis pathway. Interestingly, we found that expression of miR-375 inhibited expression of PDK1, which is a direct target of miR-375, followed by suppression of Akt phosphorylation. Further analysis by gene expression microarray revealed that 14-3-3ζ, a potent antiapoptotic gene, was significantly downregulated at both the mRNA and protein levels in cells transfected with miR-375. The activity of a luciferase reporter containing the miR-375 binding sequence at the 3′ untranslated region (UTR) of 14-3-3ζ mRNA was repressed by the ectopic expression of miR-375, suggesting that miR-375 targets the 3′ UTR of 14-3-3ζ. In addition, knockdown of either PDK1 or 14-3-3ζ in gastric carcinoma cells induced caspase activation, which was also observed in miR-375–transfected cells, suggesting that miR-375 may exert its proapoptotic function, at least in part, through the downregulation of PDK1 and 14-3-3ζ. Taken together, we propose that miR-375 is a candidate tumor suppressor miRNA in gastric carcinoma. Cancer Res; 70(6); 2339–49
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/0008-5472.CAN-09-2777
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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