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MicroRNA-100 regulates pancreatic cancer cells growth and sensitivity to chemotherapy through targeting FGFR3

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Tumor Biology

Abstract

We intended to investigate the role of microRNA 100 (miR-100) in regulating pancreatic cancer cells’ growth in vitro and tumor development in vivo. QTR-PCR was used to examine the expression of miR-100 in pancreatic cancer cell lines and tumor cells from human patients. Lentivirual vector containing miR-100 mimics (lv-miR-100) was used to overexpress miR-100 in MIA PaCa-2 and FCPAC-1 cells. The effects of overexpressing miR-100 on pancreatic cancer cell proliferation and chemosensitivity to cisplatin were examined by cell proliferation essay in vitro. MIA PaCa-2 cells with endogenously overexpressed miR-100 were transplanted into null mice to examine tumor growth in vivo. The predicted target of miR-100, fibroblast growth factor receptor 3 (FGFR3), was downregulated by siRNA to examine its effect on pancreatic cancer cells. We found miR-100 was markedly underexpressed in both pancreatic cancer cell lines and tumor cells from patients. In cancer cells, transfection of lv-miR-100 was able to upregulate endogenous expression of miR-100, inhibited cancer cell proliferation, and increased sensitivities to cisplatin. Overexpressing miR-100 led to significant inhibition on tumor formation in vivo. Luciferase essay showed FGFR3 was direct target of miR-100. FGFR3 was significantly downregulated by overexpressing miR-100 in pancreatic cancer cells and knocking down FGFR3 by siRNA exerted similar effect as miR-100. Our study demonstrated that miR-100 played an important role in pancreatic cancer development, possibly through targeting FGFR3. It may become a new therapeutic target for gene therapy in patients suffered from pancreatic cancer.

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Acknowledgment

This work is supported by the National Natural Science Foundation of China (No. 81160311), International Science & Technology Cooperation Program of China (NO.2014DFA31420), and the Outstanding Young Training Project of Science and Education of Guizhou Province, China. NO. [2012]177 and the China Postdoctoral Science Foundation (NO.2013M531983)

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Authors and Affiliations

  1. Department of Biliary-Hepatic Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou Province, 50004, China

    Zhipeng Li, Chao Yu, Jie Xiao, Jianxin Jiang & Chengyi Sun

  2. Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430074, China

    Xu Li, Min Wang, Feng Peng & Rui Tian

Authors
  1. Zhipeng Li
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  2. Xu Li
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  3. Chao Yu
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  4. Min Wang
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  5. Feng Peng
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  6. Jie Xiao
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  7. Rui Tian
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  8. Jianxin Jiang
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  9. Chengyi Sun
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Corresponding authors

Correspondence to Jianxin Jiang or Chengyi Sun.

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Zhipeng Li and Xu Li contributed equally to this work.

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Li, Z., Li, X., Yu, C. et al. MicroRNA-100 regulates pancreatic cancer cells growth and sensitivity to chemotherapy through targeting FGFR3. Tumor Biol. 35, 11751–11759 (2014). https://doi.org/10.1007/s13277-014-2271-8

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  • DOI: https://doi.org/10.1007/s13277-014-2271-8

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