Tumor Biology

, Volume 36, Issue 12, pp 9245–9249 | Cite as

High serum miR-183 level is associated with poor responsiveness of renal cancer to natural killer cells

  • Qunmei Zhang
  • Wenyu Di
  • Yuqian Dong
  • Guangjian Lu
  • Jian Yu
  • Jinsong Li
  • Pingfa Li
Research Article


Renal cell carcinoma (RCC) is among the most common subtype of kidney cancers, and the current therapeutic strategies are not efficient. Natural killer (NK) cells are biological agents that can induce apoptosis in a wide range of cancer cells. However, most of RCC patients exhibit resistance against the action of NK cells due to unknown mechanisms. This study is aimed to identify a biomarker that can predict the response of RCC cells to NK cell treatment. We collected 82 RCC patients and 19 healthy volunteers to detect the expression of miR-183 in blood by qPCR assays. The results revealed that serum miR-183 is significantly higher in RCC patients than in healthy controls, and its level is positively associated with the grading of RCC. Furthermore, 51Cr release assays indicated that the primary RCC cells with low serum miR-183 expression are more sensitive to the cytotoxicity of NK cells. Collectively, we demonstrated that serum miR-183 can be used to predict the response of RCC cells to the cytotoxicity induced by NK cells.


RCC miR-183 NK Immunotherapy 


  1. 1.
    Raval RR, Sharabi AB, Walker AJ, Drake CG, Sharma P. Tumor immunology and cancer immunotherapy: summary of the 2013 SITC primer. J Immunother Cancer. 2014;2:14. doi: 10.1186/2051-1426-2-14.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Galanis E, Hersh EM, Stopeck AT, Gonzalez R, Burch P, Spier C, et al. Immunotherapy of advanced malignancy by direct gene transfer of an interleukin-2 DNA/DMRIE/DOPE lipid complex: phase I/II experience. J Clin Oncol: Off J Am Soc Clin Oncol. 1999;17(10):3313–23.CrossRefGoogle Scholar
  3. 3.
    Wittig B, Marten A, Dorbic T, Weineck S, Min H, Niemitz S, et al. Therapeutic vaccination against metastatic carcinoma by expression-modulated and immunomodified autologous tumor cells: a first clinical phase I/II trial. Hum Gene Ther. 2001;12(3):267–78. doi: 10.1089/10430340150218404.CrossRefPubMedGoogle Scholar
  4. 4.
    Kawai K, Tani K, Yamashita N, Tomikawa S, Eriguchi M, Fujime M, et al. Advanced renal cell carcinoma treated with granulocyte-macrophage colony-stimulating factor gene therapy: a clinical course of the first Japanese experience. Int J Urol: Off J Jpn Urol Ass. 2002;9(8):462–6.CrossRefGoogle Scholar
  5. 5.
    Santoni M, Berardi R, Amantini C, Burattini L, Santini D, Santoni G, et al. Role of natural and adaptive immunity in renal cell carcinoma response to VEGFR-TKIs and mTOR inhibitor. Int J Cancer J Int Cancer. 2014;134(12):2772–7. doi: 10.1002/ijc.28503.CrossRefGoogle Scholar
  6. 6.
    Margolin KA. Interleukin-2 in the treatment of renal cancer. Semin Oncol. 2000;27(2):194–203.PubMedGoogle Scholar
  7. 7.
    Eckl J, Buchner A, Prinz PU, Riesenberg R, Siegert SI, Kammerer R, et al. Transcript signature predicts tissue NK cell content and defines renal cell carcinoma subgroups independent of TNM staging. J Mol Med. 2012;90(1):55–66. doi: 10.1007/s00109-011-0806-7.CrossRefPubMedGoogle Scholar
  8. 8.
    Specht HM, Ahrens N, Blankenstein C, Duell T, Fietkau R, Gaipl US, et al. Heat shock protein 70 (Hsp70) peptide activated natural killer (NK) cells for the treatment of patients with non-small cell lung cancer (NSCLC) after radiochemotherapy (RCTx)—from preclinical studies to a clinical phase II trial. Front Immunol. 2015;6:162. doi: 10.3389/fimmu.2015.00162.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Jakel CE, Vogt A, Gonzalez-Carmona MA, Schmidt-Wolf IG. Clinical studies applying cytokine-induced killer cells for the treatment of gastrointestinal tumors. J Immunol Res. 2014;2014:897214. doi: 10.1155/2014/897214.
  10. 10.
    Klingemann HG. Cellular therapy of cancer with natural killer cells—where do we stand? Cytotherapy. 2013;15(10):1185–94. doi: 10.1016/j.jcyt.2013.03.011.CrossRefPubMedGoogle Scholar
  11. 11.
    Fromm PD, Gottlieb D, Bradstock KF, Hart DN. Cellular therapy to treat haematological and other malignancies: progress and pitfalls. Pathology. 2011;43(6):605–15. doi: 10.1097/PAT.0b013e32834b6b24.CrossRefPubMedGoogle Scholar
  12. 12.
    Escudier B, Farace F, Angevin E, Charpentier F, Nitenberg G, Triebel F, et al. Immunotherapy with interleukin-2 (IL2) and lymphokine-activated natural killer cells: improvement of clinical responses in metastatic renal cell carcinoma patients previously treated with IL2. Eur J Cancer. 1994;30A(8):1078–83.CrossRefPubMedGoogle Scholar
  13. 13.
    Arai S, Meagher R, Swearingen M, Myint H, Rich E, Martinson J, et al. Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial. Cytotherapy. 2008;10(6):625–32. doi: 10.1080/14653240802301872.CrossRefPubMedGoogle Scholar
  14. 14.
    Grange C, Collino F, Tapparo M, Camussi G. Oncogenic micro-RNAs and renal cell carcinoma. Front Oncol. 2014;4:49. doi: 10.3389/fonc.2014.00049.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Zhang QH, Sun HM, Zheng RZ, Li YC, Zhang Q, Cheng P, et al. Meta-analysis of microRNA-183 family expression in human cancer studies comparing cancer tissues with noncancerous tissues. Gene. 2013;527(1):26–32. doi: 10.1016/j.gene.2013.06.006.CrossRefPubMedGoogle Scholar
  16. 16.
    Xu F, Zhang H, Su Y, Kong J, Yu H, Qian B. Up-regulation of microRNA-183-3p is a potent prognostic marker for lung adenocarcinoma of female non-smokers. Clin Trans Oncol: Off Pub Fed Span Oncol Soc Natl Cancer Ins Mex. 2014. doi: 10.1007/s12094-014-1183-9.Google Scholar
  17. 17.
    Wang L, Zhu MJ, Ren AM, Wu HF, Han WM, Tan RY, et al. A ten-MicroRNA signature identified from a genome-wide MicroRNA expression profiling in human epithelial ovarian cancer. PLoS One. 2014;9(5):e96472. doi: 10.1371/journal.pone.0096472.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Zhou T, Zhang GJ, Zhou H, Xiao HX, Li Y. Overexpression of microRNA-183 in human colorectal cancer and its clinical significance. Eur J Gastroenterol Hepatol. 2014;26(2):229–33. doi: 10.1097/MEG.0000000000000002.CrossRefPubMedGoogle Scholar
  19. 19.
    Yoshino H, Seki N, Itesako T, Chiyomaru T, Nakagawa M, Enokida H. Aberrant expression of microRNAs in bladder cancer. Nat Rev Urol. 2013;10(7):396–404. doi: 10.1038/nrurol.2013.113.CrossRefPubMedGoogle Scholar
  20. 20.
    Torres-Martin M, Lassaletta L, de Campos JM, Isla A, Gavilan J, Pinto GR, et al. Global profiling in vestibular schwannomas shows critical deregulation of microRNAs and upregulation in those included in chromosomal region 14q32. PLoS One. 2013;8(6):e65868. doi: 10.1371/journal.pone.0065868.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Sarver AL, Li L, Subramanian S. MicroRNA miR-183 functions as an oncogene by targeting the transcription factor EGR1 and promoting tumor cell migration. Cancer Res. 2010;70(23):9570–80. doi: 10.1158/0008-5472.CAN-10-2074.CrossRefPubMedGoogle Scholar
  22. 22.
    Ueno K, Hirata H, Shahryari V, Deng G, Tanaka Y, et al. MicroRNA-183 is an oncogene targeting Dkk-3 and SMAD4 in prostate cancer. Br J Cancer. 2013;108(8):1659–67. doi: 10.1038/bjc.2013.125.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Donatelli SS, Zhou JM, Gilvary DL, Eksioglu EA, Chen X, Cress WD, et al. TGF-beta-inducible microRNA-183 silences tumor-associated natural killer cells. Proc Natl Acad Sci U S A. 2014;111(11):4203–8. doi: 10.1073/pnas.1319269111.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Zen K, Zhang CY. Circulating microRNAs: a novel class of biomarkers to diagnose and monitor human cancers. Med Res Rev. 2012;32(2):326–48. doi: 10.1002/med.20215.CrossRefPubMedGoogle Scholar
  25. 25.
    Ranghino A, Cantaluppi V, Grange C, Vitillo L, Fop F, Biancone L, et al. Endothelial progenitor cell-derived microvesicles improve neovascularization in a murine model of hindlimb ischemia. Int J Immunopathol Pharmacol. 2012;25(1):75–85.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Qunmei Zhang
    • 1
  • Wenyu Di
    • 2
  • Yuqian Dong
    • 3
  • Guangjian Lu
    • 3
  • Jian Yu
    • 2
  • Jinsong Li
    • 2
  • Pingfa Li
    • 4
  1. 1.Blood Transfusion RoomThe First Affiliated Hospital of Xinxiang Medical UniversityWeihuiChina
  2. 2.Department of PathologyThe First Affiliated Hospital of Xinxiang Medical UniversityWeihuiChina
  3. 3.Clinical LaboratoryThe First Affiliated Hospital of Xinxiang Medical UniversityWeihuiChina
  4. 4.College of Clinical LaboratoryXinxiang Medical University, Molecular Diagnostics and Medical Inspection Technology Collaborative Innovation Center in Henan ProvinceXinxiangChina

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