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Crucial microRNAs and genes in metformin’s anti-pancreatic cancer effect explored by microRNA-mRNA integrated analysis

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Summary

Despite great improvements in surgical procedures and chemotherapy, pancreatic cancer remains one of the most aggressive and fatal human malignancies, with a low 5-year survival rate. Therefore, novel therapeutic strategies for the prevention and treatment of pancreatic cancer are urgently needed. The present study aimed to investigate the mechanisms by which metformin exerts its anticancer effects on the microRNA-mRNA interactions in human pancreatic cancer. Microarray and systematic analyses revealed that the anti-pancreatic cancer effects of metformin were correlated with 3 up-regulated microRNAs and 4 of their target mRNAs. In addition, the microarray and systematic analyses ultimately demonstrated that 3 microRNAs regulated 4 key mRNAs in a sub-pathway of pancreatic cancer and then affected growth, angiogenesis, and apoptosis. This finding may provide a deeper understanding of the mechanisms by which metformin suppresses proliferation and angiogenesis and promotes apoptosis in pancreatic cancer cells. Collectively, this experiment improves the understanding of the mechanisms by which metformin suppresses pancreatic cancer and indicates that metformin, the most commonly used drug for the treatment of diabetes mellitus, may be a promising candidate agent for the treatment of pancreatic cancer.

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Funding

This work was supported by the National Nature Scientific Foundation of China (No. 81372613 and 81,302,057), The National High Technology Research and Development Program of China (No. 2014AA020609), and the Youth Science Foundation of Heilongjiang Province (No. QC2012C042).

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Authors and Affiliations

  1. Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China

    Yilong Li, Le Li, Guangquan Zhang, Yongwei Wang, Hua Chen, Rui Kong, Shangha Pan & Bei Sun

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  1. Yilong Li
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  2. Le Li
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  3. Guangquan Zhang
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  4. Yongwei Wang
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  5. Hua Chen
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  6. Rui Kong
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  7. Shangha Pan
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  8. Bei Sun
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Correspondence to Bei Sun.

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Conflict of interest

Yilong Li declares that he has no conflicts of interest. Le Li declares that he has no conflicts of interest. Guangquan Zhang declares that he has no conflicts of interest. Yongwei Wang declares that he has no conflicts of interest. Hua Chen declares that he has no conflicts of interest. Rui Kong declares that he has no conflicts of interest. Shangha Pan declares that he has no conflicts of interest. Bei Sun declares that he has no conflicts of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in this study.

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Li, Y., Li, L., Zhang, G. et al. Crucial microRNAs and genes in metformin’s anti-pancreatic cancer effect explored by microRNA-mRNA integrated analysis. Invest New Drugs 36, 20–27 (2018). https://doi.org/10.1007/s10637-017-0508-2

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  • DOI: https://doi.org/10.1007/s10637-017-0508-2

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