Tumor Biology

, Volume 35, Issue 12, pp 11751–11759 | Cite as

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

  • Zhipeng Li
  • Xu Li
  • Chao Yu
  • Min Wang
  • Feng Peng
  • Jie Xiao
  • Rui Tian
  • Jianxin JiangEmail author
  • Chengyi SunEmail author
Research Article


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.


miR-100 Cisplatin FGFR3 Pancreatic cancer 



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)

Conflicts of interest



  1. 1.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA: Cancer J Clin. 2010;60:277–300.CrossRefGoogle Scholar
  2. 2.
    Chen W, Zheng R, Zhang S, Zhao P, Li G, et al. Report of incidence and mortality in China cancer registries, 2009. Chin J Cancer Res = Chung-kuo yen cheng yen chiu. 2013;25:10–21.Google Scholar
  3. 3.
    Hirata K, Egawa S, Kimura Y, Nobuoka T, Oshima H, et al. Current status of surgery for pancreatic cancer. Dig Surg. 2007;24:137–47.PubMedCrossRefGoogle Scholar
  4. 4.
    Gillen S, Schuster T, Meyer Zum Buschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7:e1000267.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Pillai RS. MicroRNA function: multiple mechanisms for a tiny RNA? RNA. 2005;11:1753–61.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857–66.PubMedCrossRefGoogle Scholar
  7. 7.
    Feng W, Feng Y. MicroRNAs in neural cell development and brain diseases. Sci Chin Life Sci. 2011;54:1103–12.CrossRefGoogle Scholar
  8. 8.
    Bian S, Sun T. Functions of noncoding RNAs in neural development and neurological diseases. Mol Neurobiol. 2011;44:359–73.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Papagiannakopoulos T, Kosik KS. MicroRNAs: regulators of oncogenesis and stemness. BMC Med. 2008;6:15.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Blandino G, Fazi F, Donzelli S, Kedmi M, Sas-Chen A, et al. Tumor suppressor microRNAs: a novel non-coding alliance against cancer. FEBS Lett. 2014;32:74–81.Google Scholar
  11. 11.
    Palanichamy JK, Rao DS. miRNA dysregulation in cancer: towards a mechanistic understanding. Front Gen. 2014;5:54.Google Scholar
  12. 12.
    Leite KR, Sousa-Canavez JM, Reis ST, Tomiyama AH, Camara-Lopes LH, et al. Change in expression of miR-let7c, miR-100, and miR-218 from high grade localized prostate cancer to metastasis. Urol Oncol. 2011;29:265–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Reis ST, Timoszczuk LS, Pontes-Junior J, Viana N, Silva IA, et al. The role of micro RNAs let7c, 100 and 218 expression and their target RAS, C-MYC, BUB1, RB, SMARCA5, LAMB3 and Ki-67 in prostate cancer. Clinics. 2013;68:652–7.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Gebeshuber CA, Martinez J. miR-100 suppresses IGF2 and inhibits breast tumorigenesis by interfering with proliferation and survival signaling. Oncogene. 2013;32:3306–10.PubMedCrossRefGoogle Scholar
  15. 15.
    Chen D, Sun Y, Yuan Y, Han Z, Zhang P, Chen D, et al. PLoS Genet. 2014;10:e1004177.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Nagaraja AK, Creighton CJ, Yu Z, Zhu H, Gunaratne PH, et al. A link between mir-100 and FRAP1/mTOR in clear cell ovarian cancer. Mol Endocrinol. 2010;24:447–63.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Peng DX, Luo M, Qiu LW, He YL, Wang XF. Prognostic implications of microRNA-100 and its functional roles in human epithelial ovarian cancer. Oncol Rep. 2012;27:1238–44.PubMedCentralPubMedGoogle Scholar
  18. 18.
    Radulovich N, Qian JY, Tsao MS. Human pancreatic duct epithelial cell model for KRAS transformation. Methods Enzymol. 2008;439:1–13.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhang L, Mizumoto K, Sato N, Ogawa T, Kusumoto M, et al. Quantitative determination of apoptotic death in cultured human pancreatic cancer cells by propidium iodide and digitonin. Cancer Lett. 1999;142:129–37.PubMedCrossRefGoogle Scholar
  20. 20.
    Jung DE, Wen J, Oh T, Song SY. Differentially expressed microRNAs in pancreatic cancer stem cells. Pancreas. 2011;40:1180–7.PubMedCrossRefGoogle Scholar
  21. 21.
    LaConti JJ, Shivapurkar N, Preet A, Deslattes Mays A, Peran I, et al. Tissue and serum microRNAs in the Kras(G12D) transgenic animal model and in patients with pancreatic cancer. PLoS One. 2011;6:e20687.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Panarelli NC, Chen YT, Zhou XK, Kitabayashi N, Yantiss RK. MicroRNA expression aids the preoperative diagnosis of pancreatic ductal adenocarcinoma. Pancreas. 2012;41:685–90.PubMedCentralPubMedGoogle Scholar
  23. 23.
    Giroux V, Dagorn JC, Iovanna JL. A review of kinases implicated in pancreatic cancer. Pancreatol: Off J Int Assoc Pancreatol. 2009;9:738–54.CrossRefGoogle Scholar
  24. 24.
    Yamanaka Y, Friess H, Buchler M, Beger HG, Uchida E, et al. Overexpression of acidic and basic fibroblast growth factors in human pancreatic cancer correlates with advanced tumor stage. Cancer Res. 1993;53:5289–96.PubMedGoogle Scholar
  25. 25.
    Kuwahara K, Sasaki T, Kuwada Y, Murakami M, Yamasaki S, et al. Expressions of angiogenic factors in pancreatic ductal carcinoma: a correlative study with clinicopathologic parameters and patient survival. Pancreas. 2003;26:344–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Hammel P, Mornex F, Deplanque G, Mitry E, Levy P, et al. Oral tyrosine kinase inhibitor masitinib in combination with gemcitabine in patients with advanced pancreatic cancer: a multicenter phase II study. J Clin Oncol. 2009;27:4617.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Zhipeng Li
    • 1
  • Xu Li
    • 2
  • Chao Yu
    • 1
  • Min Wang
    • 2
  • Feng Peng
    • 2
  • Jie Xiao
    • 1
  • Rui Tian
    • 2
  • Jianxin Jiang
    • 1
    Email author
  • Chengyi Sun
    • 1
    Email author
  1. 1.Department of Biliary-Hepatic SurgeryAffiliated Hospital of Guiyang Medical CollegeGuiyangChina
  2. 2.Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Personalised recommendations