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MiRNA-221-3p desensitizes pancreatic cancer cells to 5-fluorouracil by targeting RB1

Tumor Biology volume 37, pages 16053–16063 (2016)Cite this article

Abstract

Pancreatic cancer is a highly lethal disease due to its rapid dissemination and resistance to conventional chemotherapy. MicroRNAs (miRNAs) are emerging as novel regulators of chemoresistance, which modulate the expression of drug resistance-related genes. MiRNA-221 has been reported to be associated with chemoresistance in various types of cancer. But the detailed molecular mechanism about miR-221-3p regulating 5-fluorouracil (5-FU) resistance in human pancreatic cancer remains to be clarified. In this study, we investigated the association between miR-221-3p expression and 5-FU sensitivity. Studies on pancreatic cancer cell lines suggested an increased 5-FU resistance with miR-221-3p over-expression. In addition, the results indicated that miR-221-3p down-regulated RB1 expression by directly binding to its 3′-UTR and therefore caused increased several aspects of pancreatic cancer pathogenesis, including proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Collectively, our findings revealed the important role of miR-221-3p in promoting 5-FU resistance of pancreatic cancer cells and provided a potential therapeutic target for pancreatic cancer.

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Acknowledgments

The authors thank Ming tai Chen and Zheng yi Zhang from IBMS of PUMC for technical assistance. This work was supported by grants from the National Natural Science Foundation of China (31371322, to J.Y.; 91440111, to J.Y.; 31571523, to Y.N.M.)

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Affiliations

  1. Institute of Molecular Medicine, Medical School, Henan University, KaiFeng, 475000, China

    Lijun Zhao, Lanlan Wang, Yuanyuan Zhang & Guotao Sun

  2. State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China

    Lijun Zhao, Xueju Wei, Siqi Liu, Yanmin Si, Hualu Zhao, Fang Wang, Jia Yu & Yanni Ma

  3. Department of Gynecologic Oncology, Chongqing Cancer Institute, Chongqing, 400030, China

    Dongling Zou

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  1. Lijun Zhao
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Correspondence to Yanni Ma or Guotao Sun.

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Lijun Zhao and Dongling Zou contributed equally to this work.

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Zhao, L., Zou, D., Wei, X. et al. MiRNA-221-3p desensitizes pancreatic cancer cells to 5-fluorouracil by targeting RB1. Tumor Biol. 37, 16053–16063 (2016). https://doi.org/10.1007/s13277-016-5445-8

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  • DOI: https://doi.org/10.1007/s13277-016-5445-8

Keywords

  • Drug resistance
  • 5-Fluorouracil
  • miR-221-3p
  • RB1
  • Pancreatic cancer