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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2018 | Research

Aberrant miRNAs expressed in HER-2 negative breast cancers patient

Authors: Cornelia Braicu, Lajos Raduly, Gabriela Morar-Bolba, Roxana Cojocneanu, Ancuta Jurj, Laura-Ancuta Pop, Valentina Pileczki, Cristina Ciocan, Alin Moldovan, Alexandru Irimie, Alexandru Eniu, Patriciu Achimas-Cadariu, Angelo Paradiso, Ioana Berindan-Neagoe

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

Abstract

Background

Breast cancer is a highly heterogeneous pathology, exhibiting a number of subtypes commonly associated with a poor outcome. Due to their high stability, microRNAs are often regarded as non-invasive cancer biomarkers, having an expression pattern specific for their ‘cell of origin’.

Method

Triple negative breast cancer (TNBC: ER-, PR-, Her-2-) and double positive breast cancer (DPBC: ER+, PR+, Her-2) miRNA expression patterns were obtained by analysis of the TCGA (The Cancer Genome Atlas) data, followed by PCR-array analysis on plasma samples from 20 TNBC patients, 14 DPBC patients and 11 controls.

Results

Three downregulated and nine upregulated miRNAs were obtained from the TNBC analysis. Five overexpressed miRNAs were identified in the DPBC group. Four of the dysregulated miRNAs (miR-10a, miR-125b, miR-210 and miR-489) were common for both groups. The cluster miR-17-92 (miR-17, miR-20a, miR-20b, and miR-93), along with miR-130, miR-22 and miR-29a/c, were found to differentiate between TNBC and DPBC. A panel of five transcripts (miR-10a, miR-125, miR-193b, miR-200b and miR-489) was validated in a new set of plasma samples. The overlapping of TCGA and plasma profiling data revealed miR-200b, miR-200c, miR-210 and miR-29c as common signature. MiR-200b was validated on additional normal and tumor tissue samples. The expression level of this transcript from the TCGA data was correlated with lung and bone metastatic genes.

Conclusion

The miR-200b presents a great potential for the future advancements in the diagnostic/prognostic and therapeutic approach of TNBC, along with other coding or non-coding transcripts. However, this needs to be further integrated in a regulatory network that acts in conjunction with other markers that affect the patients’ prognosis or response to therapy.

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Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86. https://doi.org/10.1002/ijc.29210.CrossRefPubMed

Chiorean R, Braicu C, Berindan-Neagoe I. Another review on triple negative breast cancer. Are we on the right way towards the exit from the labyrinth? Breast. 2013;22:1026–33. https://doi.org/10.1016/j.breast.2013.08.007.CrossRefPubMed

Eastlack SC, Alahari SK. MicroRNA and breast Cancer: understanding pathogenesis, improving management. Noncoding RNA. 2015;1:17–43. https://doi.org/10.3390/ncrna1010017.CrossRefPubMedPubMedCentral

Gasparini P, Cascione L, Fassan M, Lovat F, Guler G, Balci S, Irkkan C, Morrison C, Croce CM, Shapiro CL, Huebner K. microRNA expression profiling identifies a four microRNA signature as a novel diagnostic and prognostic biomarker in triple negative breast cancers. Oncotarget. 2014;5:1174–84.CrossRefPubMedPubMedCentral

Jiang HL, Sun HF, Gao SP, Li LD, Hu X, Wu J, Jin W. Loss of RAB1B promotes triple-negative breast cancer metastasis by activating TGF-beta/SMAD signaling. Oncotarget. 2015.

Braicu C, Chiorean R, Irimie A, Chira S, Tomuleasa C, Neagoe E, Paradiso A, Achimas-Cadariu P, Lazar V, Berindan-Neagoe I. Novel insight into triple-negative breast cancers, the emerging role of angiogenesis, and antiangiogenic therapy. Expert Rev Mol Med. 2016;18:e18. https://doi.org/10.1017/erm.2016.17.CrossRefPubMed

Foroni C, Broggini M, Generali D, Damia G. Epithelial-mesenchymal transition and breast cancer: role, molecular mechanisms and clinical impact. Cancer Treat Rev. 2012;38:689–97. https://doi.org/10.1016/j.ctrv.2011.11.001.CrossRefPubMed

Irimie AI, Braicu C, Cojocneanu-Petric R, Berindan-Neagoe I, Campian RS. Novel technologies for oral squamous carcinoma biomarkers in diagnostics and prognostics. Acta Odontol Scand. 2015;73:161–8. https://doi.org/10.3109/00016357.2014.986754.CrossRefPubMed

D'Ippolito E, Iorio MV. MicroRNAs and triple negative breast cancer. Int J Mol Sci. 2013;14:22202–20. https://doi.org/10.3390/ijms141122202.CrossRefPubMedPubMedCentral

10.

Braicu C, Calin GA, Berindan-Neagoe I. MicroRNAs and cancer therapy - from bystanders to major players. Curr Med Chem. 2013;20:3561–73.CrossRefPubMed

11.

Braicu C, Cojocneanu-Petric R, Chira S, Truta A, Floares A, Petrut B, Achimas-Cadariu P, Berindan-Neagoe I. Clinical and pathological implications of miRNA in bladder cancer. Int J Nanomedicine. 2015;10:791–800. https://doi.org/10.2147/ijn.s72904.CrossRefPubMedPubMedCentral

12.

Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857–66. https://doi.org/10.1038/nrc1997.CrossRefPubMed

13.

Gotte M. MicroRNAs in breast cancer pathogenesis. Minerva Ginecol. 2010;62:559–71.PubMed

14.

Volinia S, Galasso M, Sana ME, Wise TF, Palatini J, Huebner K, Croce CM. Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA. Proc Natl Acad Sci U S A. 2012;109:3024–9. https://doi.org/10.1073/pnas.1200010109.CrossRefPubMedPubMedCentral

15.

Ling H, Vincent K, Pichler M, Fodde R, Berindan-Neagoe I, Slack FJ, Calin GA. Junk DNA and the long non-coding RNA twist in cancer genetics. Oncogene. 2015. https://doi.org/10.1038/onc.2014.456.CrossRefPubMedPubMedCentral

16.

Braicu C, Catana C, Calin GA, Berindan-Neagoe I. NCRNA combined therapy as future treatment option for cancer. Curr Pharm Des. 2014;20:6565–74.CrossRefPubMed

17.

Chang HT, Li SC, Ho MR, Pan HW, Ger LP, Hu LY, Yu SY, Li WH, Tsai KW. Comprehensive analysis of microRNAs in breast cancer. BMC Genomics. 2012;13(Suppl 7):S18. https://doi.org/10.1186/1471-2164-13-S7-S18.CrossRefPubMedPubMedCentral

18.

Redis RS, Berindan-Neagoe I, Pop VI, Calin GA. Non-coding RNAs as theranostics in human cancers. J Cell Biochem. 2012;113:1451–9. https://doi.org/10.1002/jcb.24038.CrossRefPubMedPubMedCentral

19.

Schou JV, Johansen JS, Nielsen D, Rossi S. Circulating microRNAs as prognostic and predictive biomarkers in patients with colorectal Cancer. Noncoding RNA. 2016;2. https://doi.org/10.3390/ncrna2020005.CrossRefPubMedCentral

20.

Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;101:2087–92. https://doi.org/10.1111/j.1349-7006.2010.01650.x.CrossRefPubMed

21.

Berindan-Neagoe I, Monroig Pdel C, Pasculli B, Calin GA. MicroRNAome genome: a treasure for cancer diagnosis and therapy. CA Cancer J Clin. 2014;64:311–36. https://doi.org/10.3322/caac.21244.CrossRefPubMedPubMedCentral

22.

Berindan-Neagoe I, Calin GA. Molecular pathways: microRNAs, cancer cells, and microenvironment. Clin Cancer Res. 2014;20:6247–53. https://doi.org/10.1158/1078-0432.ccr-13-2500.CrossRefPubMedPubMedCentral

23.

Tomuleasa C, Braicu C, Irimie A, Craciun L, Berindan-Neagoe I. Nanopharmacology in translational hematology and oncology. Int J Nanomedicine. 2014;9:3465–79. https://doi.org/10.2147/ijn.s60488.CrossRefPubMedPubMedCentral

24.

Catana CS, Pichler M, Giannelli G, Mader RM, Berindan-Neagoe I. Non-coding RNAs, the Trojan horse in two-way communication between tumor and stroma in colorectal and hepatocellular carcinoma. Oncotarget. 2017;8:29519–34. https://doi.org/10.18632/oncotarget.15706.CrossRefPubMedPubMedCentral

25.

Redis RS, Sieuwerts AM, Look MP, Tudoran O, Ivan C, Spizzo R, Zhang X, de Weerd V, Shimizu M, Ling H, Buiga R, Pop V, Irimie A, et al. CCAT2, a novel long non-coding RNA in breast cancer: expression study and clinical correlations. Oncotarget. 2013;4:1748–62. https://doi.org/10.18632/oncotarget.1292.CrossRefPubMedPubMedCentral

26.

Irimie AI, Zimta AA, Ciocan C, Mehterov N, Dudea D, Braicu C, Berindan-Neagoe I. The unforeseen non-coding RNAs in head and neck Cancer. Genes (Basel). 2018;9. https://doi.org/10.3390/genes9030134.CrossRefPubMedCentral

27.

Chu A, Robertson G, Brooks D, Mungall AJ, Birol I, Coope R, Ma Y, Jones S, Marra MA. Large-scale profiling of microRNAs for the Cancer genome atlas. Nucleic Acids Res. 2016;44:e3. https://doi.org/10.1093/nar/gkv808.CrossRefPubMed

28.

Klimov S, Rida PC, Aleskandarany MA, Green AR, Ellis IO, Janssen EA, Rakha EA, Aneja R. Novel immunohistochemistry-based signatures to predict metastatic site of triple-negative breast cancers. Br J Cancer. 2017;117:826–34. https://doi.org/10.1038/bjc.2017.224.CrossRefPubMedPubMedCentral

29.

Scimeca M, Antonacci C, Toschi N, Giannini E, Bonfiglio R, Buonomo CO, Pistolese CA, Tarantino U, Bonanno E. Breast osteoblast-like cells: a reliable early marker for bone metastases from breast Cancer. Clin Breast Cancer. 2018;18:e659–e69. https://doi.org/10.1016/j.clbc.2017.11.020.CrossRefPubMed

30.

Huntsman DG, Ladanyi M. The molecular pathology of cancer: from pan-genomics to post-genomics. J Pathol. 2018;244:509–11. https://doi.org/10.1002/path.5057.CrossRefPubMed

31.

van Schooneveld E, Wouters MC, Van der Auwera I, Peeters DJ, Wildiers H, Van Dam PA, Vergote I, Vermeulen PB, Dirix LY, Van Laere SJ. Expression profiling of cancerous and normal breast tissues identifies microRNAs that are differentially expressed in serum from patients with (metastatic) breast cancer and healthy volunteers. Breast Cancer Res. 2012;14:R34. https://doi.org/10.1186/bcr3127.CrossRefPubMedPubMedCentral

32.

Conger AK, Martin EC, Yan TJ, Rhodes LV, Hoang VT, La J, Anbalagan M, Burks HE, Rowan BG, Nephew KP, Collins-Burow BM, Burow ME. Argonaute 2 expression correlates with a luminal B breast Cancer subtype and induces estrogen receptor alpha isoform variation. Noncoding RNA. 2016;2. https://doi.org/10.3390/ncrna2030008.CrossRefPubMedCentral

33.

Krutilina R, Sun W, Sethuraman A, Brown M, Seagroves TN, Pfeffer LM, Ignatova T, Fan M. MicroRNA-18a inhibits hypoxia-inducible factor 1α activity and lung metastasis in basal breast cancers. Breast Cancer Research : BCR. 2014;16:R78. https://doi.org/10.1186/bcr3693.CrossRefPubMedPubMedCentral

34.

Zhang HF, Xu LY, Li EM. A family of pleiotropically acting microRNAs in cancer progression, miR-200: potential cancer therapeutic targets. Curr Pharm Des. 2014;20:1896–903.CrossRefPubMed

35.

Braicu C, Tudoran O, Balacescu L, Catana C, Neagoe E, Berindan-Neagoe I, Ionescu C. The significance of PDGF expression in serum of colorectal carcinoma patients--correlation with Duke's classification. Can PDGF become a potential biomarker? Chirurgia (Bucur). 2013;108:849–54.

36.

Truong HH, Xiong J, Ghotra VP, Nirmala E, Haazen L, Le Devedec SE, Balcioglu HE, He S, Snaar-Jagalska BE, Vreugdenhil E, Meerman JH, van de Water B, Danen EH. Beta1 integrin inhibition elicits a prometastatic switch through the TGFbeta-miR-200-ZEB network in E-cadherin-positive triple-negative breast cancer. Sci Signal. 2014;7:ra15. https://doi.org/10.1126/scisignal.2004751.CrossRefPubMed

37.

Madhavan D, Peng C, Wallwiener M, Zucknick M, Nees J, Schott S, Rudolph A, Riethdorf S, Trumpp A, Pantel K, Sohn C, Chang-Claude J, Schneeweiss A, et al. Circulating miRNAs with prognostic value in metastatic breast cancer and for early detection of metastasis. Carcinogenesis. 2016. https://doi.org/10.1093/carcin/bgw008.CrossRefPubMed

38.

Zhang G, Zhang W, Li B, Stringer-Reasor E, Chu C, Sun L, Bae S, Chen D, Wei S, Jiao K, Yang W-H, Cui R, Liu R, et al. MicroRNA-200c and microRNA- 141 are regulated by a FOXP3-KAT2B axis and associated with tumor metastasis in breast cancer. Breast Cancer Res : BCR. 2017; 19: 73. doi: https://doi.org/10.1186/s13058-017-0858-x.

39.

Lopez-Serra P, Esteller M. DNA methylation-associated silencing of tumor-suppressor microRNAs in cancer. Oncogene. 2012;31:1609–22. https://doi.org/10.1038/onc.2011.354.CrossRefPubMed

40.

Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, Brabletz T. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 2008;9:582–9. https://doi.org/10.1038/embor.2008.74.CrossRefPubMedPubMedCentral

41.

Chen Y, Gorski DH. Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood. 2008;111:1217–26. https://doi.org/10.1182/blood-2007-07-104133.CrossRefPubMedPubMedCentral

42.

Song SJ, Pandolfi PP. miR-22 in tumorigenesis. Cell Cycle. 2014;13:11–2. https://doi.org/10.4161/cc.27027.CrossRefPubMed

43.

Wu Z, Huang X, Huang X, Zou Q, Guo Y. The inhibitory role of Mir-29 in growth of breast cancer cells. J Exp Clin Cancer Res. 2013;32:98. https://doi.org/10.1186/1756-9966-32-98.CrossRefPubMedPubMedCentral

44.

Jiang H, Zhang G, Wu JH, Jiang CP. Diverse roles of miR-29 in cancer (review). Oncol Rep. 2014;31:1509–16. https://doi.org/10.3892/or.2014.3036.CrossRefPubMed

45.

Cochrane DR, Jacobsen BM, Connaghan KD, Howe EN, Bain DL, Richer JK. Progestin regulated miRNAs that mediate progesterone receptor action in breast cancer. Mol Cell Endocrinol. 2012;355:15–24. https://doi.org/10.1016/j.mce.2011.12.020.CrossRefPubMedPubMedCentral

46.

Alsidawi S, Malek E, Driscoll JJ. MicroRNAs in brain metastases: potential role as diagnostics and therapeutics. Int J Mol Sci. 2014;15:10508–26. https://doi.org/10.3390/ijms150610508.CrossRefPubMedPubMedCentral

47.

Yang W, Wei J, Sun T, Liu F. Effects of knockdown of miR-210 in combination with ionizing radiation on human hepatoma xenograft in nude mice. Radiat Oncol. 2013;8:102. https://doi.org/10.1186/1748-717X-8-102.CrossRefPubMedPubMedCentral

48.

Tang Y, Zhou X, Ji J, Chen L, Cao J, Luo J, Zhang S. High expression levels of miR-21 and miR-210 predict unfavorable survival in breast cancer: a systemic review and meta-analysis. Int J Biol Markers. 2015;30:e347–58. https://doi.org/10.5301/jbm.5000160.CrossRefPubMed

49.

Hong L, Yang J, Han Y, Lu Q, Cao J, Syed L. High expression of miR-210 predicts poor survival in patients with breast cancer: a meta-analysis. Gene. 2012;507:135–8. https://doi.org/10.1016/j.gene.2012.07.025.CrossRefPubMed

50.

Jung EJ, Santarpia L, Kim J, Esteva FJ, Moretti E, Buzdar AU, Di Leo A, Le XF, Bast RC, Jr., Park ST, Pusztai L, Calin GA. Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. Cancer 2012; 118: 2603–2614. doi: https://doi.org/10.1002/cncr.26565.CrossRefPubMed

51.

Toyama T, Kondo N, Endo Y, Sugiura H, Yoshimoto N, Iwasa M, Takahashi S, Fujii Y, Yamashita H. High expression of microRNA-210 is an independent factor indicating a poor prognosis in Japanese triple-negative breast cancer patients. Jpn J Clin Oncol. 2012;42:256–63. https://doi.org/10.1093/jjco/hys001.CrossRefPubMed

52.

Lu L, Mao X, Shi P, He B, Xu K, Zhang S, Wang J. MicroRNAs in the prognosis of triple-negative breast cancer: a systematic review and meta-analysis. Medicine (Baltimore). 2017;96:e7085. https://doi.org/10.1097/md.0000000000007085.CrossRef

Title: Aberrant miRNAs expressed in HER-2 negative breast cancers patient
Authors: Cornelia Braicu
Lajos Raduly
Gabriela Morar-Bolba
Roxana Cojocneanu
Ancuta Jurj
Laura-Ancuta Pop
Valentina Pileczki
Cristina Ciocan
Alin Moldovan
Alexandru Irimie
Alexandru Eniu
Patriciu Achimas-Cadariu
Angelo Paradiso
Ioana Berindan-Neagoe
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-018-0920-2

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