MicroRNA-34a Mediates the Autocrine Signaling of PAR2-Activating Proteinase and Its Role in Colonic Cancer Cell Proliferation

被引：47

作者：

Ma, Yiming ^{[1
]}

Bao-Han, Wuyun ^{[1
]}

Lv, Xue ^{[1
]}

Su, Yuntao ^{[3
]}

Zhao, Xinhua ^{[1
]}

Yin, Yongmei ^{[3
]}

Zhang, Xingmao ^{[2
]}

Zhou, Zhixiang ^{[2
]}

MacNaughton, Wallace K. ^{[4
,5
]}

Wang, Hongying ^{[1
]}

机构：

[1] Chinese Acad Med Sci, State Key Lab Mol Oncol, Inst Canc, Canc Hosp,Peking Union Med Coll, Beijing 100730, Peoples R China

[2] Chinese Acad Med Sci, Dept Gastrointestinal Canc Surg, Inst Canc, Canc Hosp,Peking Union Med Coll, Beijing 100730, Peoples R China

[3] Nanjing Med Univ, Affiliated Hosp 1, Nanjing, Jiangsu, Peoples R China

[4] Univ Calgary, Inflammat Res Network, Calgary, AB, Canada

[5] Univ Calgary, Dept Physiol & Biophys, Calgary, AB, Canada

来源：

PLOS ONE | 2013年 / 8卷 / 08期

关键词：

PROTEASE-ACTIVATED RECEPTOR-2; EXPRESSION; TRYPSIN; GROWTH; FIBRONECTIN; STIMULATION; ASSOCIATION; CARCINOMA; PROMOTES; ADHESION;

D O I：

10.1371/journal.pone.0072383

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The tumor microenvironment is replete with proteinases. As a sensor of proteinases, proteinase activated receptor 2 (PAR(2)) plays critical roles in tumorigenesis. We showed that PAR(2) and its activating proteinase were coexpressed in different colon cancer cell lines, including HT29. Inactivating proteinase or knockdown of PAR(2) significantly not only reduced cell proliferation in vitro but also inhibited tumorigenicity of HT29 in vivo. In addition, activation of PAR(2) promoted DNA synthesis and upregulated Cyclin D1 activity at both transcriptional and post-transcriptional levels. Further studies showed that miRNA-34a mediated PAR(2)-induced Cyclin D1 upregulation. Inhibition of miR-34a partially abolished the suppression of Cyclin D1 induced by PAR(2) deficiency. In addition, we showed that TGF-beta contributed to the regulation of miR-34a by PAR(2). Finally, in colorectal carcinoma samples, upregulation of PAR(2) 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.

引用

页数：11

共 40 条

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