Abstract:
:Tumor initiation and growth depend on its microenvironment in which cancer-associated fibroblasts (CAFs) in tumor stroma play an important role. Prostaglandin E2 (PGE2) and interleukin (IL)-6 signal pathways are involved in the crosstalk between tumor and stromal cells. However, how PGE2-mediated signaling modulates this crosstalk remains unclear. Here, we show that microRNA (miR)-149 links PGE2 and IL-6 signaling in mediating the crosstalk between tumor cells and CAFs in gastric cancer (GC). miR-149 inhibited fibroblast activation by targeting IL-6 and miR-149 expression was substantially suppressed in the CAFs of GC. miR-149 negatively regulated CAFs and their effect on GC development both in vitro and in vivo. CAFs enhanced epithelial-to-mesenchymal transition (EMT) and the stem-like properties of GC cells in a miR-149-IL-6-dependent manner. In addition to IL-6, PGE2 receptor 2 (PTGER2/EP2) was revealed as another potential target of miR-149 in fibroblasts. Furthermore, H. pylori infection, a leading cause of human GC, was able to induce cyclooxygenase-2 (COX-2)/PGE2 signaling and to enhance PGE2 production, resulting in the hypermethylation of miR-149 in CAFs and increased IL-6 secretion. Our findings indicate that miR-149 mediates the crosstalk between tumor cells and CAFs in GC and highlight the potential of interfering miRNAs in stromal cells to improve cancer therapy.
journal_name
Cell Resjournal_title
Cell researchauthors
Li P,Shan JX,Chen XH,Zhang D,Su LP,Huang XY,Yu BQ,Zhi QM,Li CL,Wang YQ,Tomei S,Cai Q,Ji J,Li JF,Chouchane L,Yu YY,Sun FZ,Xu ZH,Liu BY,Zhu ZGdoi
10.1038/cr.2015.51subject
Has Abstractpub_date
2015-05-01 00:00:00pages
588-603issue
5eissn
1001-0602issn
1748-7838pii
cr201551journal_volume
25pub_type
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