Tumor Biology

, Volume 37, Issue 12, pp 16053–16063 | Cite as

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

  • Lijun Zhao
  • Dongling Zou
  • Xueju Wei
  • Lanlan Wang
  • Yuanyuan Zhang
  • Siqi Liu
  • Yanmin Si
  • Hualu Zhao
  • Fang Wang
  • Jia Yu
  • Yanni Ma
  • Guotao Sun
Original Article
First Online:
Received:
Accepted:

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.

Keywords

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

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.)

Compliance with ethical standards

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Lijun Zhao
    • 1
    • 2
  • Dongling Zou
    • 3
  • Xueju Wei
    • 2
  • Lanlan Wang
    • 1
  • Yuanyuan Zhang
    • 1
  • Siqi Liu
    • 2
  • Yanmin Si
    • 2
  • Hualu Zhao
    • 2
  • Fang Wang
    • 2
  • Jia Yu
    • 2
  • Yanni Ma
    • 2
  • Guotao Sun
    • 1
  1. 1.Institute of Molecular Medicine, Medical SchoolHenan UniversityKaiFengChina
  2. 2.State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical SciencesChinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegeBeijingChina
  3. 3.Department of Gynecologic OncologyChongqing Cancer InstituteChongqingChina

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