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

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Tumor Biology

Abstract

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.

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Acknowledgments

This study was supported by The National Nature Science Foundation of China (No. 30973470, No. 81172334, and No. 81400664).

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Authors and Affiliations

  1. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuai Fu Yuan, Hu Tong, Beijing, 100730, China

    Cuiping Wang, Yang Sun, Huanwen Wu, Shuangni Yu, Li Zhang, Yunxiao Meng, Mingyang Liu, Haiyan Yang, Pingping Liu, Xinxin Mao, Zhaohui Lu & Jie Chen

  2. Department of Pathology, Beijing Tsinghua Changgung Hospital, Medical Center, Tsinghua University, No. 168 Litang Road, Changping District, Beijing, 100730, China

    Cuiping Wang

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  1. Cuiping Wang
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Correspondence to Jie Chen.

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Wang, C., Sun, Y., Wu, H. et al. Elevated miR-483-3p expression is an early event and indicates poor prognosis in pancreatic ductal adenocarcinoma. Tumor Biol. 36, 9447–9456 (2015). https://doi.org/10.1007/s13277-015-3690-x

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  • DOI: https://doi.org/10.1007/s13277-015-3690-x

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