MicroRNA-34a mediates the autocrine signaling of PAR2-activating proteinase and its role in colonic cancer cell proliferation.
The tumor microenvironment is replete with proteinases. As a sensor of proteinases, proteinase activated receptor 2 (PAR2) plays critical roles in tumorigenesis. We showed that PAR2 and its activating proteinase were coexpressed in different colon cancer cell lines, including HT29. Inactivating prot...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3753253?pdf=render |
| _version_ | 1818701579205738496 |
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| author | Yiming Ma Wuyun Bao-Han Xue Lv Yuntao Su Xinhua Zhao Yongmei Yin Xingmao Zhang Zhixiang Zhou Wallace K MacNaughton Hongying Wang |
| author_facet | Yiming Ma Wuyun Bao-Han Xue Lv Yuntao Su Xinhua Zhao Yongmei Yin Xingmao Zhang Zhixiang Zhou Wallace K MacNaughton Hongying Wang |
| author_sort | Yiming Ma |
| collection | DOAJ |
| description | The tumor microenvironment is replete with proteinases. As a sensor of proteinases, proteinase activated receptor 2 (PAR2) plays critical roles in tumorigenesis. We showed that PAR2 and its activating proteinase were coexpressed in different colon cancer cell lines, including HT29. Inactivating proteinase or knockdown of PAR2 significantly not only reduced cell proliferation in vitro but also inhibited tumorigenicity of HT29 in vivo. In addition, activation of PAR2 promoted DNA synthesis and upregulated Cyclin D1 activity at both transcriptional and post-transcriptional levels. Further studies showed that miRNA-34a mediated PAR2-induced Cyclin D1 upregulation. Inhibition of miR-34a partially abolished the suppression of Cyclin D1 induced by PAR2 deficiency. In addition, we showed that TGF-β contributed to the regulation of miR-34a by PAR2. Finally, in colorectal carcinoma samples, upregulation of PAR2 and downregulation of miR-34a were significantly correlated with grade and lymphomatic metastasis. Our findings provide the first evidence that miRNA mediates autocrine proteinase signaling-mediated cancer cell proliferation. |
| first_indexed | 2024-12-17T15:23:05Z |
| format | Article |
| id | doaj.art-ac50492789b74333b911156ac6771eb2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T15:23:05Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ac50492789b74333b911156ac6771eb22022-12-21T21:43:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7238310.1371/journal.pone.0072383MicroRNA-34a mediates the autocrine signaling of PAR2-activating proteinase and its role in colonic cancer cell proliferation.Yiming MaWuyun Bao-HanXue LvYuntao SuXinhua ZhaoYongmei YinXingmao ZhangZhixiang ZhouWallace K MacNaughtonHongying WangThe tumor microenvironment is replete with proteinases. As a sensor of proteinases, proteinase activated receptor 2 (PAR2) plays critical roles in tumorigenesis. We showed that PAR2 and its activating proteinase were coexpressed in different colon cancer cell lines, including HT29. Inactivating proteinase or knockdown of PAR2 significantly not only reduced cell proliferation in vitro but also inhibited tumorigenicity of HT29 in vivo. In addition, activation of PAR2 promoted DNA synthesis and upregulated Cyclin D1 activity at both transcriptional and post-transcriptional levels. Further studies showed that miRNA-34a mediated PAR2-induced Cyclin D1 upregulation. Inhibition of miR-34a partially abolished the suppression of Cyclin D1 induced by PAR2 deficiency. In addition, we showed that TGF-β contributed to the regulation of miR-34a by PAR2. Finally, in colorectal carcinoma samples, upregulation of PAR2 and downregulation of miR-34a were significantly correlated with grade and lymphomatic metastasis. Our findings provide the first evidence that miRNA mediates autocrine proteinase signaling-mediated cancer cell proliferation.http://europepmc.org/articles/PMC3753253?pdf=render |
| spellingShingle | Yiming Ma Wuyun Bao-Han Xue Lv Yuntao Su Xinhua Zhao Yongmei Yin Xingmao Zhang Zhixiang Zhou Wallace K MacNaughton Hongying Wang MicroRNA-34a mediates the autocrine signaling of PAR2-activating proteinase and its role in colonic cancer cell proliferation. PLoS ONE |
| title | MicroRNA-34a mediates the autocrine signaling of PAR2-activating proteinase and its role in colonic cancer cell proliferation. |
| title_full | MicroRNA-34a mediates the autocrine signaling of PAR2-activating proteinase and its role in colonic cancer cell proliferation. |
| title_fullStr | MicroRNA-34a mediates the autocrine signaling of PAR2-activating proteinase and its role in colonic cancer cell proliferation. |
| title_full_unstemmed | MicroRNA-34a mediates the autocrine signaling of PAR2-activating proteinase and its role in colonic cancer cell proliferation. |
| title_short | MicroRNA-34a mediates the autocrine signaling of PAR2-activating proteinase and its role in colonic cancer cell proliferation. |
| title_sort | microrna 34a mediates the autocrine signaling of par2 activating proteinase and its role in colonic cancer cell proliferation |
| url | http://europepmc.org/articles/PMC3753253?pdf=render |
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