Skip to main content
Top
Published in: Tumor Biology 12/2016

01-12-2016 | Review

Involvement of microRNAs in HER2 signaling and trastuzumab treatment

Authors: Ling Mao, Ai-jun Sun, Jian-zhong Wu, Jin-hai Tang

Published in: Tumor Biology | Issue 12/2016

Login to get access

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.
Literature
2.
go back to reference 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.CrossRef 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.CrossRef
4.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
8.
10.
go back to reference 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.CrossRef 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.CrossRef
12.
go back to reference 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. 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.
17.
go back to reference 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.CrossRef 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.CrossRef
20.
go back to reference 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.PubMedPubMedCentral 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.PubMedPubMedCentral
21.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
27.
go back to reference 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.CrossRef 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.CrossRef
38.
42.
go back to reference 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.PubMed 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.PubMed
45.
go back to reference 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.PubMed 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.PubMed
49.
go back to reference 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.CrossRef 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.CrossRef
50.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
51.
go back to reference 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.CrossRef 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.CrossRef
53.
54.
go back to reference 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.CrossRef 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.CrossRef
56.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
59.
go back to reference 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.CrossRef 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.CrossRef
62.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
64.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
65.
66.
go back to reference 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.CrossRef 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.CrossRef
68.
go back to reference 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.PubMedPubMedCentral 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.PubMedPubMedCentral
69.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
70.
72.
go back to reference 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.CrossRef 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.CrossRef
76.
go back to reference 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.PubMed 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.PubMed
79.
81.
go back to reference 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.CrossRef 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.CrossRef
82.
go back to reference 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.CrossRef 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.CrossRef
83.
go back to reference 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.PubMed 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.PubMed
Metadata
Title
Involvement of microRNAs in HER2 signaling and trastuzumab treatment
Authors
Ling Mao
Ai-jun Sun
Jian-zhong Wu
Jin-hai Tang
Publication date
01-12-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 12/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5405-3

Other articles of this Issue 12/2016

Tumor Biology 12/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine