Aberrant plasma levels of circulating miR-16, miR-107, miR-130a and miR-146a are associated with lymph node metastasis and receptor status of breast cancer patients

Within the multicenter SUCCESS trial, we investigated the association of plasma microRNAs with different subtypes of invasive breast cancer. Six miRs (miR-16, miR-27a, miR-107, miR-130a, miR-132 and miR-146a) were selected from microarray profiling and further validated in plasma of 111 breast cancer patients before and after chemotherapy and 46 healthy women by quantitative real-time PCR. Plasma levels of miR-16 (p = 0.0001), miR-27a (p = 0.039) and miR-132 (p = 0.020) were higher in breast cancer patients before chemotherapy than healthy women. With the exception of miR-16, the increased levels of miR-27a (p = 0.035) and miR-132 (p = 0.025) decreased after chemotherapy to those observed in healthy women. Levels of miR-16 (p = 0.019), miR-107 (p = 0.036), miR-130a (p = 0.027) and miR-146a (p = 0.047) were different between lymph node -positive and -negative patients, while the levels of miR-130a (p = 0.001) and miR-146a (p = 0.025) also differed between HER2-positive and -negative status. Estrogen-receptor negative tumors displayed higher concentrations of circulating miR-107 than their counterparts (p = 0.035). However, overexpression of miR-107 in MCF-7 cells did not downregulate estrogen receptor protein. Altered expression levels of miR-107 influenced the migration and invasion behavior of MCF-7 and MDA-MB-231 cells. Our data indicate differential concentrations of plasma miR-16, miR-107, miR-130a and miR-146a in different breast cancer subtypes, suggesting a potential role of these miRs in breast cancer biology and tumor progression.

[1]  Na Han,et al.  miR-107 Activates ATR/Chk1 Pathway and Suppress Cervical Cancer Invasion by Targeting MCL1 , 2014, PloS one.

[2]  M. Rugge,et al.  Circulating miR-182 is a biomarker of colorectal adenocarcinoma progression , 2014, Oncotarget.

[3]  Jiang Li,et al.  Tumor-derived exosomes promote tumor progression and T-cell dysfunction through the regulation of enriched exosomal microRNAs in human nasopharyngeal carcinoma , 2014, Oncotarget.

[4]  Qiang Hu,et al.  Circulating miR-148b and miR-133a as biomarkers for breast cancer detection , 2014, Oncotarget.

[5]  F. Yu,et al.  miR-27a regulates endothelial differentiation of breast cancer stem like cells , 2014, Oncogene.

[6]  G. Calin,et al.  Clinical relevance of circulating cell-free microRNAs in cancer , 2014, Nature Reviews Clinical Oncology.

[7]  Deng-feng Li,et al.  MiRNA-107 inhibits proliferation and migration by targeting CDK8 in breast cancer. , 2014, International journal of clinical and experimental medicine.

[8]  D. Amadori,et al.  Tumor-induced osteoclast miRNA changes as regulators and biomarkers of osteolytic bone metastasis. , 2013, Cancer cell.

[9]  H. Schwarzenbach.  Circulating nucleic acids as biomarkers in breast cancer , 2013, Breast Cancer Research.

[10]  K. Pritchard.  Endocrine therapy: is the first generation of targeted drugs the last? , 2013, Journal of internal medicine.

[11]  Fan Yang,et al.  Retinoic acid-induced HOXA5 expression is co-regulated by HuR and miR-130a. , 2013, Cellular signalling.

[12]  P. Perumal,et al.  Overexpression of circulating miRNA-21 and miRNA-146a in plasma samples of breast cancer patients. , 2013, Indian journal of biochemistry & biophysics.

[13]  X. Chen,et al.  MicroRNA-107 Inhibits U87 Glioma Stem Cells Growth and Invasion , 2013, Cellular and Molecular Neurobiology.

[14]  Shuai Li,et al.  MicroRNA-132 is frequently down-regulated in ductal carcinoma in situ (DCIS) of breast and acts as a tumor suppressor by inhibiting cell proliferation. , 2013, Pathology, research and practice.

[15]  Xiaolong Wang,et al.  The Oncogene Metadherin Modulates the Apoptotic Pathway Based on the Tumor Necrosis Factor Superfamily Member TRAIL (Tumor Necrosis Factor-related Apoptosis-inducing Ligand) in Breast Cancer* , 2013, The Journal of Biological Chemistry.

[16]  T. Blondal,et al.  Assessing sample and miRNA profile quality in serum and plasma or other biofluids. , 2013, Methods.

[17]  F. Yu,et al.  MiR-27 as a Prognostic Marker for Breast Cancer Progression and Patient Survival , 2012, PloS one.

[18]  Xi Chen,et al.  Serum microRNA profiling and breast cancer risk: the use of miR-484/191 as endogenous controls. , 2012, Carcinogenesis.

[19]  M. Beckmann,et al.  Invasive Breast Cancer: Recognition of Molecular Subtypes , 2011, Breast Care.

[20]  Klaus Pantel,et al.  Cell-free nucleic acids as biomarkers in cancer patients , 2011, Nature Reviews Cancer.

[21]  R. Lidereau,et al.  Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers , 2011, EMBO molecular medicine.

[22]  Lorenzo Ferraro,et al.  Estrogen receptor alpha controls a gene network in luminal-like breast cancer cells comprising multiple transcription factors and microRNAs. , 2010, The American journal of pathology.

[23]  Muneesh Tewari,et al.  Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). , 2010, Methods.

[24]  K. J. Sweeney,et al.  MicroRNAs as Novel Biomarkers for Breast Cancer , 2009, Journal of oncology.

[25]  Robert L Moritz,et al.  Exosomes: proteomic insights and diagnostic potential , 2009, Expert review of proteomics.

[26]  Nectarios Koziris,et al.  DIANA-microT web server: elucidating microRNA functions through target prediction , 2009, Nucleic Acids Res..

[27]  Kedar S Vaidya,et al.  Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. , 2009, Cancer research.

[28]  D. Bartel.  MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

[29]  G. Calin,et al.  MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. , 2009, Expert opinion on biological therapy.

[30]  Doron Betel,et al.  The microRNA.org resource: targets and expression , 2007, Nucleic Acids Res..

[31]  Leonard D. Goldstein,et al.  MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype , 2007, Genome Biology.

[32]  G. M. Nagaraja,et al.  Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics , 2006, Oncogene.

[33]  F. Slack,et al.  Oncomirs — microRNAs with a role in cancer , 2006, Nature Reviews Cancer.

[34]  M. Byrom,et al.  Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis , 2005, Nucleic acids research.

[35]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.