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MLH1 as a Direct Target of MiR-155 and a Potential Predictor of Favorable Prognosis in Pancreatic Cancer

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Background

The regulation of Mut L homologue 1 (MLH1) expression by microRNA (miR)-155 and its prognostic significance in pancreatic cancer (PC) remain to be elucidated. This study aimed to address the issues.

Methods

MiR-155 mimics and inhibitor were transfected to PC cell lines, Panc-1 and Capan-1. Expression of MLH1 was subsequently evaluated. Then, luciferase activity was detected after miR-155 mimics and pRL-TK plasmids containing wild-type and mutant 3′UTRs of MLH1 mRNA were co-transfected. Finally, immunohistochemical staining for MLH1 was performed in PC samples.

Results

Transfection of miR-155 mimics and inhibitor led to reversely altered protein expressions of miR-155 and MLH1, whereas the corresponding mRNA expressions were similar. A significant decrease in luciferase activity in the cells transfected with the wild-type pRL-TK plasmid was shown in contrast to those transfected with the mutant one. In addition, MLH1 was less expressed in tumor than in para-tumor tissues of PC. Extensive MLH1 expression was significantly associated with favorable differentiation and less lymph node metastasis. MLH1 expression was found to be a prognosticator in univariate analysis, and being of marginally significant impact in multivariate test.

Conclusions

MLH1 might serve as a direct target of miR-155 and a potential prognosis predictor in PC.

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Acknowledgments

This study was supported by the National Laboratory of Molecular Biology Special Foundation (2060204), Beijing Municipal Natural Science Foundation (7100003), and research special fund for public welfare industry of health (201202007), China.

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Authors and Affiliations

  1. Department of General Surgery, National Laboratory of Medical Molecular Biology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China

    Wen-Jing Liu, Yu-Pei Zhao, Tai-Ping Zhang, Li Zhou, Lei You, Ge Chen & Hong Shu

  2. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China

    Quan-Cai Cui & Wei-Xun Zhou

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  1. Wen-Jing Liu
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  2. Yu-Pei Zhao
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  4. Li Zhou
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Correspondence to Yu-Pei Zhao.

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Liu, WJ., Zhao, YP., Zhang, TP. et al. MLH1 as a Direct Target of MiR-155 and a Potential Predictor of Favorable Prognosis in Pancreatic Cancer. J Gastrointest Surg 17, 1399–1405 (2013). https://doi.org/10.1007/s11605-013-2230-5

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  • DOI: https://doi.org/10.1007/s11605-013-2230-5

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