期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 287, 期 2, 页码 1397-1405出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M111.288662
关键词
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资金
- Ministry of Education, Culture, Sports, Science, and Technology
- National Institute of Biomedical Innovation
- Japan Society for the Promotion of Science through Council for Science and Technology Policy
- Grants-in-Aid for Scientific Research [10J04220, 21115008] Funding Source: KAKEN
Normal epithelial cells regulate the secretion of autocrine and paracrine factors that prevent aberrant growth of neighboring cells, leading to healthy development and normal metabolism. One reason for tumor initiation is considered to be a failure of this homeostatic cell competitive system. Here we identify tumor-suppressive microRNAs (miRNAs) secreted by normal cells as anti-proliferative signal entities. Culture supernatant of normal epithelial prostate PNT-2 cells attenuated proliferation of PC-3M-luc cells, prostate cancer cells. Global analysis of miRNA expression signature revealed that a variety of tumor-suppressive miRNAs are released from PNT-2 cells. Of these miRNAs, secretory miR-143 could induce growth inhibition exclusively in cancer cells in vitro and in vivo. These results suggest that secretory tumor-suppressive miRNAs can act as a death signal in a cell competitive process. This study provides a novel insight into a tumor initiation mechanism.
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