Elevated miR-483-3p expression is an early event and indicates poor prognosis in pancreatic ductal adenocarcinoma

Elevated miR-483-3p expression is an early event and indicates poor prognosis in pancreatic ductal adenocarcinoma
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miR-483-3p 表达升高是早期事件,表明胰腺导管腺癌预后不良

DOI:
10.1007/s13277-015-3690-x
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发表时间:
2015-06
期刊:
影响因子:
--
通讯作者:
Chen Jie
Chen Jie
中科院分区:
--
文献类型:
--
作者:
Wang Cuiping;Sun Yang;Wu Huanwen;Yu Shuangni;Zhang Li;Meng Yunxiao;Liu Mingyang;Yang Haiyan;Liu Pingping;Mao Xinxin;Lu Zhaohui;Chen Jie

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MiR-483-3p has been reported to be widely involved in diverse human malignancies. However, the exact role of miR-483-3p remains elusive in pancreatic ductal adenocarcinoma (PDAC). The objective of this study is to determine the expression pattern and clinical implications of miR-483-3p in PDAC. MiR-483-3p levels were evaluated by locked nucleic acid-in situ hybridization (LNA-ISH) in a tissue microarray including 63 PDAC tumors and 10 normal pancreatic tissues, followed by evaluation in an independent set of 117 pairs of matched PDAC tumors and adjacent tumor-free pancreatic tissues. Expression of miR-483-3p was further evaluated in pancreatic intra-epithelial neoplasias (PanINs) and chronic pancreatitis (CP). The impact of miR-483-3p on cell proliferation, growth, and anchorage-independent colony formation was also assessed in vitro and in vivo. Microarray analysis revealed that miR-483-3p was positively stained in 61 (96.8 %) PDAC samples, but not detectable in normal pancreatic duct tissue. In the 117 PDAC samples, 100 % were miR-483-3p positive, with 55.6 % (65/117) strongly positive, compared to only 13.7 % (16/117) weakly positive in adjacent normal pancreatic duct tissues. MiR-483-3p expression was associated with tumor grading (p< 0.05) and was an independent predictor of poor overall survival in multivariate analysis (HR = 2.584; 95 % CI = 1.268–5.264). Moreover, from PanIN1 to PanIN3, the rate of strong miR-483-3p-positive staining was 0 % (0/39), 14.8 % (4/27), and 87.5 % (14/16), respectively. Six (54.5 %) CP samples were only weakly stained for miR-483-3p. Inhibition of miR-483-3p suppressed cell proliferation, growth, and colony formation in vitro and decreased tumor cell growth in nude mouse xenografts in vivo. These results suggest that aberrant miR-483-3p expression is an early event in PDAC tumorigenesis and is associated with tumor differentiation and prognosis. It also may be a potential target for PDAC molecular therapeutics.
DOI: 10.1038/nature03702
发表时间: 2005-06-09
期刊: NATURE
影响因子: 64.8
作者:
Lu, J;Getz, G;Golub, TR
通讯作者: Golub, TR
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发表时间: 2013-11
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发表时间: 1993-10
影响因子: 4.1
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