Advertisement

Tumor Biology

, Volume 37, Issue 12, pp 15437–15446 | Cite as

Involvement of microRNAs in HER2 signaling and trastuzumab treatment

  • Ling Mao
  • Ai-jun Sun
  • Jian-zhong Wu
  • Jin-hai Tang
Review

Abstract

The prognostic value of HER2 has been demonstrated in many human cancer types such us breast cancer, gastric cancer and ovarian cancer. Trastuzumab is the first anti-HER2 monoclonal antibody that has remarkably improved outcomes of patients with HER2-positive breast cancer. For HER2-positive metastatic gastric cancers, the addition of trastuzumab to traditional chemotherapy also significantly prolonged overall survival. However, intrinsic and acquired resistance to trastuzumab is common and results in disease progression. HER2 signaling network and mechanisms underlying the resistance have been broadly investigated in order to develop strategy to overcome the dilemma. Increasing evidence indicates that microRNAs (miRNA), a group of small non-coding RNAs, are involved in HER2 signaling and trastuzumab treatment. This review summarizes all the miRNAs that target HER2 and describes their activity on biological processes. Moreover, miRNAs that regulate trastuzumab resistance and relevant molecular mechanisms are highlighted. MiRNA signatures associated with HER2, miRNAs that mediate trastuzumab activity, and potential miRNA biomarkers of trastuzumab sensitivity are also discussed.

Keywords

MicroRNA HER2 Trastuzumab 

Notes

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81272470).

Compliance with ethical standards

Conflicts of interest

None

References

  1. 1.
    Bader AG, Brown D, Stoudemire J, Lammers P. Developing therapeutic microRNAs for cancer. Gene Ther. 2011;18(12):1121–6. doi: 10.1038/gt.2011.79.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Bai WD et al. MiR-200c suppresses TGF-beta signaling and counteracts trastuzumab resistance and metastasis by targeting ZNF217 and ZEB1 in breast cancer. Int J Cancer J Int du Cancer. 2014;135(6):1356–68. doi: 10.1002/ijc.28782.CrossRefGoogle Scholar
  3. 3.
    Bailey ST, Westerling T, Brown M. Loss of estrogen-regulated microRNA expression increases HER2 signaling and is prognostic of poor outcome in luminal breast cancer. Cancer Res. 2015;75(2):436–45. doi: 10.1158/0008-5472.CAN-14-1041.CrossRefPubMedGoogle Scholar
  4. 4.
    Bang YJ et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97. doi: 10.1016/S0140-6736(10)61121-X.CrossRefPubMedGoogle Scholar
  5. 5.
    Berns K et al. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell. 2007;12(4):395–402. doi: 10.1016/j.ccr.2007.08.030.CrossRefPubMedGoogle Scholar
  6. 6.
    Bertoli G, Cava C, Castiglioni I. MicroRNAs: new biomarkers for diagnosis, prognosis, therapy prediction and therapeutic tools for breast cancer. Theranostics. 2015;5(10):1122–43. doi: 10.7150/thno.11543.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bhattacharyya M, Nath J, Bandyopadhyay S. MicroRNA signatures highlight new breast cancer subtypes. Gene. 2015;556(2):192–8. doi: 10.1016/j.gene.2014.11.053.CrossRefPubMedGoogle Scholar
  8. 8.
    Boulbes DR, Chauhan GB, Jin Q, Bartholomeusz C, Esteva FJ. CD44 expression contributes to trastuzumab resistance in HER2-positive breast cancer cells. Breast Cancer Res Treat. 2015;151(3):501–13. doi: 10.1007/s10549-015-3414-3.CrossRefPubMedGoogle Scholar
  9. 9.
    Brennan PJ, Kumagai T, Berezov A, Murali R, Greene MI. HER2/neu: mechanisms of dimerization/oligomerization. Oncogene. 2000;19(53):6093–101. doi: 10.1038/sj.onc.1203967.CrossRefPubMedGoogle Scholar
  10. 10.
    Browne BC et al. Inhibition of IGF1R activity enhances response to trastuzumab in HER-2-positive breast cancer cells. Ann Oncol : Off J Eur Soc Med Oncol/ ESMO. 2011;22(1):68–73. doi: 10.1093/annonc/mdq349.CrossRefGoogle Scholar
  11. 11.
    Browne BC et al. Evaluation of IGF1R and phosphorylated IGF1R as targets in HER2-positive breast cancer cell lines and tumours. Breast Cancer Res Treat. 2012;136(3):717–27. doi: 10.1007/s10549-012-2260-9.CrossRefPubMedGoogle Scholar
  12. 12.
    Bueno-de-Mesquita JM et al. Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER). Lancet Oncol. 2007;8(12):1079–87. doi: 10.1016/S1470-2045(07)70346-7.
  13. 13.
    Castaneda CA, Cortes-Funes H, Gomez HL, Ciruelos EM. The phosphatidyl inositol 3-kinase/AKT signaling pathway in breast cancer. Cancer Metastasis Rev. 2010;29(4):751–9. doi: 10.1007/s10555-010-9261-0.CrossRefPubMedGoogle Scholar
  14. 14.
    Castiglioni F, Tagliabue E, Campiglio M, Pupa SM, Balsari A, Menard S. Role of exon-16-deleted HER2 in breast carcinomas. Endocr-Relat Cancer. 2006;13(1):221–32. doi: 10.1677/erc.1.01047.CrossRefPubMedGoogle Scholar
  15. 15.
    Chandarlapaty S et al. Frequent mutational activation of the PI3K-AKT pathway in trastuzumab-resistant breast cancer. Clin Cancer Res: Off J Am Assoc Cancer Res. 2012;18(24):6784–91. doi: 10.1158/1078-0432.CCR-12-1785.CrossRefGoogle Scholar
  16. 16.
    Chen H et al. Preliminary validation of ERBB2 expression regulated by miR-548d-3p and miR-559. Biochem Biophys Res Commun. 2009;385(4):596–600. doi: 10.1016/j.bbrc.2009.05.113.CrossRefPubMedGoogle Scholar
  17. 17.
    Cobleigh MA et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol: Off J Am Soc Clin Oncol. 1999;17(9):2639–48.CrossRefGoogle Scholar
  18. 18.
    Dai X, Chen A, Bai Z. Integrative investigation on breast cancer in ER, PR and HER2-defined subgroups using mRNA and miRNA expression profiling. Sci Rep. 2014;4:6566. doi: 10.1038/srep06566.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    De Cola A et al. miR-205-5p-mediated downregulation of ErbB/HER receptors in breast cancer stem cells results in targeted therapy resistance. Cell Death Dis. 2015;6:e1823. doi: 10.1038/cddis.2015.192.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    De Mattos-Arruda L et al. MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients. Oncotarget. 2015;6(35):37269–80. doi: 10.18632/oncotarget.5495.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Dhillon J, Astanehe A, Lee C, Fotovati A, Hu K, Dunn SE. The expression of activated Y-box binding protein-1 serine 102 mediates trastuzumab resistance in breast cancer cells by increasing CD44+ cells. Oncogene. 2010;29(47):6294–300. doi: 10.1038/onc.2010.365.CrossRefPubMedGoogle Scholar
  22. 22.
    Eger A et al. DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene. 2005;24(14):2375–85. doi: 10.1038/sj.onc.1208429.CrossRefPubMedGoogle Scholar
  23. 23.
    Epis MR, Giles KM, Barker A, Kendrick TS, Leedman PJ. miR-331-3p regulates ERBB-2 expression and androgen receptor signaling in prostate cancer. J Biol Chem. 2009;284(37):24696–704. doi: 10.1074/jbc.M109.030098.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Epis MR, Barker A, Giles KM, Beveridge DJ, Leedman PJ. The RNA-binding protein HuR opposes the repression of ERBB-2 gene expression by microRNA miR-331-3p in prostate cancer cells. J Biol Chem. 2011;286(48):41442–54. doi: 10.1074/jbc.M111.301481.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Esteva FJ et al. PTEN, PIK3CA, p-AKT, and p-p70S6K status: association with trastuzumab response and survival in patients with HER2-positive metastatic breast cancer. Am J Pathol. 2010;177(4):1647–56. doi: 10.2353/ajpath.2010.090885.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Eto K et al. The microRNA-21/PTEN pathway regulates the sensitivity of HER2-positive gastric cancer cells to trastuzumab. Ann Surg Oncol. 2014;21(1):343–50. doi: 10.1245/s10434-013-3325-7.CrossRefPubMedGoogle Scholar
  27. 27.
    Eto K et al. The sensitivity of gastric cancer to trastuzumab is regulated by the miR-223/FBXW7 pathway. Int J Cancer J Int du Cancer. 2015;136(7):1537–45. doi: 10.1002/ijc.29168.CrossRefGoogle Scholar
  28. 28.
    Fang C, Zhao Y, Guo B. MiR-199b-5p targets HER2 in breast cancer cells. J Cell Biochem. 2013;114(7):1457–63. doi: 10.1002/jcb.24487.CrossRefPubMedGoogle Scholar
  29. 29.
    Gallardo A et al. Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3K/Akt pathway are related with trastuzumab resistance in HER2 breast carcinomas. Br J Cancer. 2012;106(8):1367–73. doi: 10.1038/bjc.2012.85.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Gong C et al. Up-regulation of miR-21 mediates resistance to trastuzumab therapy for breast cancer. J Biol Chem. 2011;286(21):19127–37. doi: 10.1074/jbc.M110.216887.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Graus-Porta D, Beerli RR, Daly JM, Hynes NE. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J. 1997;16(7):1647–55. doi: 10.1093/emboj/16.7.1647.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Hammond SM. An overview of microRNAs. Adv Drug Deliv Rev. 2015;87:3–14. doi: 10.1016/j.addr.2015.05.001.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    He J et al. Reactive oxygen species regulate ERBB2 and ERBB3 expression via miR-199a/125b and DNA methylation. EMBO Rep. 2012;13(12):1116–22. doi: 10.1038/embor.2012.162.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Holbro T, Beerli RR, Maurer F, Koziczak M, Barbas 3rd CF, Hynes NE. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc Natl Acad Sci U S A. 2003;100(15):8933–8. doi: 10.1073/pnas.1537685100.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Huang X et al. Heterotrimerization of the growth factor receptors erbB2, erbB3, and insulin-like growth factor-i receptor in breast cancer cells resistant to herceptin. Cancer Res. 2010;70(3):1204–14. doi: 10.1158/0008-5472.CAN-09-3321.CrossRefPubMedGoogle Scholar
  36. 36.
    Huynh FC, Jones FE. MicroRNA-7 inhibits multiple oncogenic pathways to suppress HER2Delta16 mediated breast tumorigenesis and reverse trastuzumab resistance. PLoS One. 2014;9(12):e114419. doi: 10.1371/journal.pone.0114419.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Ichikawa T et al. Trastuzumab produces therapeutic actions by upregulating miR-26a and miR-30b in breast cancer cells. PLoS One. 2012;7(2):e31422. doi: 10.1371/journal.pone.0031422.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Jin Q, Esteva FJ. Cross-talk between the ErbB/HER family and the type I insulin-like growth factor receptor signaling pathway in breast cancer. J Mammary Gland Biol Neoplasia. 2008;13(4):485–98. doi: 10.1007/s10911-008-9107-3.CrossRefPubMedGoogle Scholar
  39. 39.
    Jung EJ et al. Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. Cancer. 2012;118(10):2603–14. doi: 10.1002/cncr.26565.CrossRefPubMedGoogle Scholar
  40. 40.
    Kaboli PJ, Rahmat A, Ismail P, Ling KH. MicroRNA-based therapy and breast cancer: a comprehensive review of novel therapeutic strategies from diagnosis to treatment. Pharmacol Res. 2015;97:104–21. doi: 10.1016/j.phrs.2015.04.015.CrossRefPubMedGoogle Scholar
  41. 41.
    Kaklamani V. A genetic signature can predict prognosis and response to therapy in breast cancer: Oncotype DX. Expert Rev Mol Diagn. 2006;6(6):803–9. doi: 10.1586/14737159.6.6.803.CrossRefPubMedGoogle Scholar
  42. 42.
    Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nature reviews. Genetics. 2010;11(9):597–610. doi: 10.1038/nrg2843.PubMedGoogle Scholar
  43. 43.
    Le XF et al. Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer. PLoS One. 2012;7(7):e41170. doi: 10.1371/journal.pone.0041170.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Lee Y, Ma J, Lyu H, Huang J, Kim A, Liu B. Role of erbB3 receptors in cancer therapeutic resistance. Acta Biochim Biophys Sin. 2014;46(3):190–8. doi: 10.1093/abbs/gmt150.CrossRefPubMedGoogle Scholar
  45. 45.
    Lehmann TP, Korski K, Ibbs M, Zawierucha P, Grodecka-Gazdecka S, Jagodzinski PP. rs12976445 variant in the pri-miR-125a correlates with a lower level of hsa-miR-125a and ERBB2 overexpression in breast cancer patients. Oncol Lett. 2013;5(2):569–73. doi: 10.3892/ol.2012.1040.PubMedGoogle Scholar
  46. 46.
    Li Z, Rana TM. Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov. 2014;13(8):622–38. doi: 10.1038/nrd4359.CrossRefPubMedGoogle Scholar
  47. 47.
    Li JT et al. MiRNA-101 inhibits breast cancer growth and metastasis by targeting CX chemokine receptor 7. Oncotarget. 2015;6(31):30818–30. doi: 10.18632/oncotarget.5067.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Liu XH et al. Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer. 2014;13:92. doi: 10.1186/1476-4598-13-92.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Lowery AJ et al. MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res: BCR. 2009;11(3):27. doi: 10.1186/bcr2257.CrossRefGoogle Scholar
  50. 50.
    Lu Y, Zi X, Zhao Y, Mascarenhas D, Pollak M. Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin. J Natl Cancer Inst. 2001;93(24):1852–7.CrossRefPubMedGoogle Scholar
  51. 51.
    Lu Y, Zi X, Pollak M. Molecular mechanisms underlying IGF-I-induced attenuation of the growth-inhibitory activity of trastuzumab (Herceptin) on SKBR3 breast cancer cells. Int J Cancer J Int du Cancer. 2004;108(3):334–41. doi: 10.1002/ijc.11445.CrossRefGoogle Scholar
  52. 52.
    Lu J et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–8. doi: 10.1038/nature03702.CrossRefPubMedGoogle Scholar
  53. 53.
    Ma T, Yang L, Zhang J. MiRNA5423p downregulation promotes trastuzumab resistance in breast cancer cells via AKT activation. Oncol Rep. 2015;33(3):1215–20. doi: 10.3892/or.2015.3713.PubMedGoogle Scholar
  54. 54.
    Miller PC, Clarke J, Koru-Sengul T, Brinkman J, El-Ashry DA. Novel MAPK-microRNA signature is predictive of hormone-therapy resistance and poor outcome in ER-positive breast cancer. Clin Cancer Res: An Off J Am Assoc Cancer Res. 2015;21(2):373–85. doi: 10.1158/1078-0432.CCR-14-2053.CrossRefGoogle Scholar
  55. 55.
    Mitra D et al. An oncogenic isoform of HER2 associated with locally disseminated breast cancer and trastuzumab resistance. Mol Cancer Ther. 2009;8(8):2152–62. doi: 10.1158/1535-7163.MCT-09-0295.CrossRefPubMedGoogle Scholar
  56. 56.
    Muller V et al. Changes in serum levels of miR-21, miR-210, and miR-373 in HER2-positive breast cancer patients undergoing neoadjuvant therapy: a translational research project within the Geparquinto trial. Breast Cancer Res Treat. 2014;147(1):61–8. doi: 10.1007/s10549-014-3079-3.CrossRefPubMedGoogle Scholar
  57. 57.
    Mulrane L, McGee SF, Gallagher WM, O’Connor DP. miRNA dysregulation in breast cancer. Cancer Res. 2013;73(22):6554–62. doi: 10.1158/0008-5472.CAN-13-1841.CrossRefPubMedGoogle Scholar
  58. 58.
    Nielsen BS et al. miR-21 expression in cancer cells may not predict resistance to adjuvant trastuzumab in primary breast cancer. Front Oncol. 2014;4:207. doi: 10.3389/fonc.2014.00207.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Nishida N et al. MicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab. Clin Cancer Res: An Off J Am Assoc Cancer Res. 2011;17(9):2725–33. doi: 10.1158/1078-0432.CCR-10-2132.CrossRefGoogle Scholar
  60. 60.
    O’Brien NA et al. Activated phosphoinositide 3-kinase/AKT signaling confers resistance to trastuzumab but not lapatinib. Mol Cancer Ther. 2010;9(6):1489–502. doi: 10.1158/1535-7163.MCT-09-1171.CrossRefPubMedGoogle Scholar
  61. 61.
    Palyi-Krekk Z, Barok M, Isola J, Tammi M, Szollosi J, Nagy P. Hyaluronan-induced masking of ErbB2 and CD44-enhanced trastuzumab internalisation in trastuzumab resistant breast cancer. Eur J Cancer. 2007;43(16):2423–33. doi: 10.1016/j.ejca.2007.08.018.CrossRefPubMedGoogle Scholar
  62. 62.
    Park YH et al. Role of HER3 expression and PTEN loss in patients with HER2-overexpressing metastatic breast cancer (MBC) who received taxane plus trastuzumab treatment. Br J Cancer. 2014;110(2):384–91. doi: 10.1038/bjc.2013.757.CrossRefPubMedGoogle Scholar
  63. 63.
    Perou CM et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52. doi: 10.1038/35021093.CrossRefPubMedGoogle Scholar
  64. 64.
    Sakurai M, Masuda M, Miki Y, Hirakawa H, Suzuki T, Sasano H. Correlation of miRNA expression profiling in surgical pathology materials, with Ki-67, HER2, ER and PR in breast cancer patients. Int J Biol Markers. 2015;30(2):e190–9. doi: 10.5301/jbm.5000141.CrossRefPubMedGoogle Scholar
  65. 65.
    Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS, Benz CC. Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem. 2007;282(2):1479–86. doi: 10.1074/jbc.M609383200.CrossRefPubMedGoogle Scholar
  66. 66.
    Shang C, YM L, Meng LR. MicroRNA-125b down-regulation mediates endometrial cancer invasion by targeting ERBB2. Med Sci Monit: Int Med J Exp Clin Res. 2012;18(4):149–55.CrossRefGoogle Scholar
  67. 67.
    Shen ZY, Zhang ZZ, Liu H, Zhao EH, Cao H. miR-375 inhibits the proliferation of gastric cancer cells by repressing ERBB2 expression. Exp Ther Med. 2014;7(6):1757–61. doi: 10.3892/etm.2014.1627.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Shen R et al. MiRNA-155 mediates TAM resistance by modulating SOCS6-STAT3 signalling pathway in breast cancer. Am J Transl Res. 2015;7(10):2115–26.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82.CrossRefPubMedGoogle Scholar
  70. 70.
    Spielmann M et al. Trastuzumab for patients with axillary-node-positive breast cancer: results of the FNCLCC-PACS 04 trial. J Clin Oncol: Off J Am Soc Clin Oncol. 2009;27(36):6129–34. doi: 10.1200/JCO.2009.23.0946.CrossRefGoogle Scholar
  71. 71.
    Vendrell JA et al. ZNF217 is a marker of poor prognosis in breast cancer that drives epithelial-mesenchymal transition and invasion. Cancer Res. 2012;72(14):3593–606. doi: 10.1158/0008-5472.CAN-11-3095.CrossRefPubMedGoogle Scholar
  72. 72.
    Vogel CL et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol : Off J Am Soc Clin Oncol. 2002;20(3):719–26.CrossRefGoogle Scholar
  73. 73.
    Wang SE et al. Transforming growth factor beta engages TACE and ErbB3 to activate phosphatidylinositol-3 kinase/Akt in ErbB2-overexpressing breast cancer and desensitizes cells to trastuzumab. Mol Cell Biol. 2008;28(18):5605–20. doi: 10.1128/MCB.00787-08.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Wang S et al. Functional cooperation of miR-125a, miR-125b, and miR-205 in entinostat-induced downregulation of erbB2/erbB3 and apoptosis in breast cancer cells. Cell Death Dis. 2013;4:e556. doi: 10.1038/cddis.2013.79.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Wang H, Jiang Y, Peng H, Chen Y, Zhu P, Huang Y. Recent progress in microRNA delivery for cancer therapy by non-viral synthetic vectors. Adv Drug Deliv Rev. 2015;81:142–60. doi: 10.1016/j.addr.2014.10.031.CrossRefPubMedGoogle Scholar
  76. 76.
    Xin H, Jiang D, Lu Z, Sun S, Kong J, Li F. Effect of miRNA-135b on proliferation, invasion and migration of triple-negative breast cancer by targeting APC. Zhonghua Yi Xue Za Zhi. 2015;95(30):2474–7.PubMedGoogle Scholar
  77. 77.
    Yagishita S et al. Chemotherapy-regulated microRNA-125-HER2 pathway as a novel therapeutic target for trastuzumab-mediated cellular cytotoxicity in small cell lung cancer. Mol Cancer Ther. 2015;14(6):1414–23. doi: 10.1158/1535-7163.MCT-14-0625.CrossRefPubMedGoogle Scholar
  78. 78.
    Yarden Y. Biology of HER2 and its importance in breast cancer. Oncology. 2001;61(2):1–13. doi: 10.1159/000055396.
  79. 79.
    Ye X et al. MiR-221 promotes trastuzumab-resistance and metastasis in HER2-positive breast cancers by targeting PTEN. BMB Rep. 2014a;47(5):268–73.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Ye XM et al. Epigenetic silencing of miR-375 induces trastuzumab resistance in HER2-positive breast cancer by targeting IGF1R. BMC Cancer. 2014b;14:134. doi: 10.1186/1471-2407-14-134.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Zhang XT, Zhang Z, Xin YN, Ma XZ, Xuan SY. Impairment of growth of gastric carcinoma by miR-133-mediated her-2 inhibition. Tumour Biol: J Int Soc Oncodevelopmental Biol Med. 2015;36(11):8925–30. doi: 10.1007/s13277-015-3637-2.CrossRefGoogle Scholar
  82. 82.
    Zhao Z, Li R, Sha S, Wang Q, Mao W, Liu T. Targeting HER3 with miR-450b-3p suppresses breast cancer cells proliferation. Cancer biology & therapy. 2014;15(10):1404–12. doi: 10.4161/cbt.29923.CrossRefGoogle Scholar
  83. 83.
    Zhao D, Sui Y, Zheng X. MiR-331-3p inhibits proliferation and promotes apoptosis by targeting HER2 through the PI3K/Akt and ERK1/2 pathways in colorectal cancer. Oncol Rep. 2016;35(2):1075–82. doi: 10.3892/or.2015.4450.PubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Nanjing Medical University Affiliated Cancer HospitalCancer Institute of Jiangsu ProvinceNanjingChina
  2. 2.Department of Thyroid and Breast SurgeryHuai’an Second People’s Hospital, Xuzhou medical universityHuai’anChina
  3. 3.Department of General Surgery, the Affiliated Jiangsu Cancer HospitalNanjing Medical UniversityNanjingChina

Personalised recommendations