The active metabolite of 5-Fluorouracil (5FU), used in the treatment of several types of cancer, acts by inhibiting the thymidylate synthase encoded by the TYMS gene, which catalyzes the rate-limiting step in DNA replication. The major failure of 5FU-based cancer therapy is the development of drug resistance. High levels of TYMS-encoded protein in cancerous tissues are predictive of poor response to 5FU treatment. Expression of TYMS is regulated by various mechanisms, including involving non-coding RNAs, both miRNAs and long non-coding RNAs (lncRNAs).

To delineate the miRNAs and lncRNAs network regulating the level of TYMS-encoded protein.

Several miRNAs targeting TYMS mRNA have been identified in colon cancers, the levels of which can be regulated to varying degrees by lncRNAs. Due to their regulation by the MALAT1 lncRNA, these miRNAs can be divided into three groups: (1) miR-197-3p, miR-203a-3p, miR-375-3p which are downregulated by MALAT1 as confirmed experimentally and the levels of these miRNAs are actually reduced in colon and gastric cancers; (2) miR-140-3p, miR-330-3p that could potentially interact with MALAT1, but not yet supported by experimental results; (3) miR-192-5p, miR-215-5p whose seed sequences do not recognize complementary response elements within MALAT1. Considering the putative MALAT1-miRNAs interaction network, attention is drawn to the potential positive feedback loop causing increased expression of MALAT1 in colon cancer and hepatocellular carcinoma, where YAP1 acts as a transcriptional co-factor which, by binding to the TCF4 transcription factor/ β-catenin complex, may increase the activation of the MALAT1 gene whereas the MALAT1 lncRNA can inhibit miR-375-3p which in turn targets YAP1 mRNA.

The network of non-coding RNAs may reduce the sensitivity of cancer cells to 5FU treatment by upregulating the level of thymidylate synthase.

• 5-FU resistance
• Capecitabine
• Chemoresistance
• Colorectal cancer
• Hippo-YAP
• Micro RNA
• Wnt beta-catenin
• ceRNA network
• miRNAs

MicroRNAs (miRNAs) are non-coding RNA molecules composed of 19–25 nucleotides that regulate gene expression and play a central role in the regulation of several immune-mediated disorders, including inflammatory bowel diseases (IBD). IBD, represented by ulcerative colitis and Crohn’s disease, is characterized by chronic intestinal inflammation associated with an increased risk of colorectal cancer (CRC). CRC is one of the most prevalent tumors in the world, and its main risk factors are obesity, physical inactivity, smoking, alcoholism, advanced age, and some eating habits, in addition to chronic intestinal inflammatory processes and the use of immunosuppressants administered to IBD patients. Recent studies have identified miRNAs associated with an increased risk of developing CRC in this population. The identification of miRNAs involved in this tumorigenic process could be useful to stratify cancer risk development for patients with IBD and to monitor and assess prognosis. Thus, the present review aimed to summarize the role of miRNAs as biomarkers for the diagnosis and prognosis of IBD-associated CRC. In the future, therapies based on miRNA modulation could be used both in clinical practice to achieve remission of the disease and restore the quality of life for patients with IBD, and to identify the patients with IBD at high risk for tumor development.

• MicroRNA
• Colorectal cancer
• Inflammatory bowel disease
• Crohn's disease
• Ulcerative colitis
• Cancer
• Diagnosis
• Prognosis
• Targets

miR-375 is a highly abundant miRNA in Merkel cell carcinoma (MCC). In other cancers, it acts as either a tumor suppressor or oncogene. While free-circulating miR-375 serves as a surrogate marker for tumor burden in patients with advanced MCC, its function within MCC cells has not been established. Nearly complete miR-375 knockdown in MCC cell lines was achieved using antagomiRs via nucleofection. The cell viability, growth characteristics, and morphology were not altered by this knockdown. miR-375 target genes and related signaling pathways were determined using Encyclopedia of RNA Interactomes (ENCORI) revealing Hippo signaling and epithelial to mesenchymal transition (EMT)-related genes likely to be regulated. Therefore, their expression was analyzed by multiplexed qRT-PCR after miR-375 knockdown, demonstrating only a limited change in expression. In summary, highly effective miR-375 knockdown in classical MCC cell lines did not significantly change the cell viability, morphology, or oncogenic signaling pathways. These observations render miR-375 an unlikely intracellular oncogene in MCC cells, thus suggesting that likely functions of miR-375 for the intercellular communication of MCC should be addressed.

• Hippo signaling
• Merkel cell carcinoma
• antagomiRs
• focal adhesion
• miR-375

The human microRNA 375 (MIR375) is significantly downregulated in human colorectal cancer (CRC) and we have previously shown that MIR375 is a CRC-associated miRNA. The metadherin (MTDH) is a candidate target gene of MIR375.

To investigate the interaction and function between MIR375 and MTDH in human CRC.

A luciferase reporter system was used to confirm the effect of MIR375 on MTDH expression. The expression levels of MIR375 and the target genes were evaluated by quantitative RT-PCR (qRT-PCR), western blotting, or immunohistochemistry.

MTDH expression was found to be upregulated in human CRC tissues compared to that in healthy controls. We show that MIR375 regulates the expression of many genes involved in the MTDH-mediated signal transduction pathways [BRAF-MAPK and phosphatidylinositol-4,5-biphosphate-3-kinase catalytic subunit alpha (PIK3CA)-AKT] in CRC cells. Upregulated MTDH expression levels were found to inhibit NF-κB inhibitor alpha, which further upregulated NFKB1 and RELA expression in CRC cells.

Our findings suggest that suppressing MIR375 expression in CRC regulates cell proliferation and angiogenesis by increasing MTDH expression. Thus, MIR375 may be of therapeutic value in treating human CRC.

• MicroRNA 375
• Metadherin
• Mitogen-activated protein kinase
• Angiogenesis
• Cell proliferation
• Colorectal cancer

• Aged
• Cell Line, Tumor
• Cell Movement/genetics
• Cell Proliferation/genetics
• Colon/pathology
• Colonic Neoplasms/genetics
• Colonic Neoplasms/pathology
• Down-Regulation
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Membrane Proteins/genetics
• MicroRNAs/metabolism
• RNA-Binding Proteins/genetics
• Rectal Neoplasms/genetics
• Rectal Neoplasms/pathology
• Rectum/pathology
• Signal Transduction/genetics
• Up-Regulation

• LDHB
• Merkel cell carcinoma
• Merkel cell polyomavirus
• cell growth
• miR-375

• 170632 Swedish Cancer Foundation
• 171133 Radiumhemmets Forskningsfonder

• Granzyme B
• Interferon-γ
• Interleukine-2
• PD-L1
• PD-L2
• biomarker
• microRNA
• nivolumab
• non-small cell lung cancer
• plasma

• SMAD-7gene polymorphisms
• colorectal cancer
• microRNA-375

• Adult
• Case-Control Studies
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Female
• Genetic Predisposition to Disease/epidemiology
• Genetic Predisposition to Disease/genetics
• Humans
• Male
• MicroRNAs/analysis
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Middle Aged
• Polymorphism, Single Nucleotide
• Smad7 Protein/analysis
• Smad7 Protein/genetics
• Smad7 Protein/metabolism

MicroRNAs (miRNAs) are small single-stranded RNAs that repress mRNA translation and trigger mRNA degradation. Of the ∼1900 miRNA-encoding genes present in the human genome, ∼250 miRNAs are reported to have changes in abundance or altered functions in colorectal cancer. Thousands of studies have documented aberrant miRNA levels in colorectal cancer, with some miRNAs reported to actively regulate tumorigenesis. A recurrent phenomenon with miRNAs is their frequent participation in feedback loops, which probably serve to reinforce or magnify biological outcomes to manifest a particular cellular phenotype. Here, we review the roles of oncogenic miRNAs (oncomiRs), tumor suppressive miRNAs (anti-oncomiRs) and miRNA regulators in colorectal cancer. Given their stability in patient-derived samples and ease of detection with standard and novel techniques, we also discuss the potential use of miRNAs as biomarkers in the diagnosis of colorectal cancer and as prognostic indicators of this disease. MiRNAs also represent attractive candidates for targeted therapies because their function can be manipulated through the use of synthetic antagonists and miRNA mimics.

Summary: This Review provides an overview of some important microRNAs and their roles in colorectal cancer.

• Cancer
• Colon
• Colorectal
• Rectal
• Tumorigenesis
• microRNA

• ROS
• colorectal cancer
• free radicals
• microRNA
• therapeutic targets

The aim of this study was to validate previously described diagnostic and prognostic microRNA expression profiles in tissue samples from patients with pancreatic cancer and other periampullary cancers.

Expression of 46 selected microRNAs was studied in formalin-fixed paraffin-embedded tissue from patients with resected pancreatic ductal adenocarcinoma (n = 165), ampullary cancer (n=59), duodenal cancer (n = 6), distal common bile duct cancer (n = 21), and gastric cancer (n = 20); chronic pancreatitis (n = 39); and normal pancreas (n = 35). The microRNAs were analyzed by PCR using the Fluidigm platform.

Twenty-two microRNAs were significantly differently expressed in patients with pancreatic cancer when compared to healthy controls and chronic pancreatitis patients; 17 miRNAs were upregulated (miR-21-5p, −23a-3p, −31-5p, −34c-5p, −93-3p, −135b-3p, −155-5p, −186-5p, −196b-5p, −203, −205-5p, −210, −222-3p, −451, −492, −614, and miR-622) and 5 were downregulated (miR-122-5p, −130b-3p, −216b, −217, and miR-375). MicroRNAs were grouped into diagnostic indices of varying complexity. Ten microRNAs associated with prognosis were identified (let-7 g, miR-29a-5p, −34a-5p, −125a-3p, −146a-5p, −187, −205-5p, −212-3p, −222-5p, and miR-450b-5p). Prognostic indices based on differences in expression of 2 different microRNAs were constructed for pancreatic and ampullary cancer combined and separately (30, 5, and 21 indices).

The study confirms that pancreatic cancer tissue has a microRNA expression profile that is different from that of other periampullary cancers, chronic pancreatitis, and normal pancreas. We identified prognostic microRNAs and microRNA indices that were associated with shorter overall survival in patients with radically resected pancreatic cancer.

The online version of this article (doi:10.1186/s40364-017-0087-6) contains supplementary material, which is available to authorized users.

• Ampullary cancer
• Biomarkers
• Pancreatic cancer
• Pancreatic ductal adenocarcinoma
• microRNA

AIM: To investigate the microRNA (miRNA) expression during histological progression from colorectal normal mucosa through adenoma to carcinoma within a lesion.

METHODS: Using microarray, the sequential changes in miRNA expression profiles were compared in colonic lesions from matched samples; histologically, non-neoplastic mucosa, adenoma, and submucosal invasive carcinoma were microdissected from a tissue sample. Cell proliferation assay was performed to observe the effect of miRNA, and its target genes were predicted using bioinformatics approaches and the expression profile of SW480 transfected with the miRNA mimics. mRNA and protein levels of the target gene in colon cancer cell lines with a mimic control or miRNA mimics were measured using qRT-PCR and Western blotting. The expression levels of miRNA and target gene in colorectal tissue samples were also measured.

RESULTS: Microarray analysis identified that the miR-320 family, including miR-320a, miR-320b, miR-320c, miR-320d and miR-320e, were differentially expressed in adenoma and submucosal invasive carcinoma. The miR-320 family, which inhibits cell proliferation, is frequently downregulated in colorectal adenoma and submucosal invasive carcinoma tissues. Seven genes including CDK6 were identified to be common in the results of gene expression array and bioinformatics analyses performed to find the target gene of the miR-320 family. We confirmed that mRNA and protein levels of CDK6 were significantly suppressed in colon cancer cell lines with miR-320 family mimics. CDK6 expression was found to increase from non-neoplastic mucosa through adenoma to submucosal invasive carcinoma tissues and showed an inverse correlation with miR-320 family expression.

CONCLUSION: MiR-320 family affects colorectal tumor proliferation by targeting CDK6, plays important role in its growth, and is considered to be a biomarker for its early detection.

• CDK6
• Colorectal cancer
• MiR-320 family
• Colorectal adenoma
• Laterally spreading type

• FZD8
• colorectal cancer
• metastasis
• microRNA-375

• Animals
• Cell Movement
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Gene Expression Profiling
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• MicroRNAs/metabolism
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Prognosis
• Receptors, Cell Surface/metabolism
• Signal Transduction
• Treatment Outcome
• Up-Regulation
• Wound Healing

• biomarker
• colorectal neoplasm
• metastasis
• miRNA
• target gene

• Animals
• Biomarkers, Tumor/genetics
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/genetics

Many studies demonstrated unique microRNA profiles in lung cancer. Nonetheless, the role and related signal pathways of miR-375 in lung cancer are largely unknown. Our study investigated relationships between carcinogenesis and miR-375 in adenocarcinoma, squamous cell carcinoma and small cell lung carcinoma to identify new molecular targets for treatment. We evaluated 723 microRNAs in microdissected cancerous cells and adjacent normal cells from 126 snap-frozen lung specimens using microarrays. We validated the expression profiles of miR-375 and its 22 putative target mRNAs in an independent cohort of 78 snap-frozen lung cancer tissues using quantitative reverse-transcriptase PCR. Moreover, we performed dual luciferase reporter assay and Western blot on 6 targeted genes (FZD8, ITGA10, ITPKB, LRP5, PIAS1 andRUNX1) in small cell lung carcinoma cell line NCI-H82. We also detected the effect of miR-375 on cell proliferation in NCI-H82. We found that miR-375 expression was significantly up-regulated in adenocarcinoma and small cell lung carcinoma but down-regulated in squamous cell carcinoma. Among the 22 putative target genes, 11 showed significantly different expression levels in at least 2 of 3 pair-wise comparisons (adenocarcinoma vs. normal, squamous cell carcinoma vs. normal or small cell lung carcinoma vs. normal). Six targeted genes had strong negative correlation with the expression level of miR-375 in small cell lung carcinoma. Further investigation revealed that miR-375 directly targeted the 3’UTR of ITPKB mRNA and over-expression of miR-375 led to significantly decreased ITPKB protein level and promoted cell growth. Thus, our study demonstrates the differential expression profiles of miR-375 in 3 subtypes of lung carcinomas and finds thatmiR-375 directly targets ITPKB and promoted cell growth in SCLC cell line.

• Adenocarcinoma/classification
• Adenocarcinoma/metabolism
• Adenocarcinoma/pathology
• Aged
• Carcinoma, Squamous Cell/classification
• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/pathology
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms/classification
• Lung Neoplasms/metabolism
• Lung Neoplasms/pathology
• Male
• MicroRNAs/metabolism
• Middle Aged
• Neoplasm Proteins/biosynthesis
• RNA, Neoplasm/metabolism
• Small Cell Lung Carcinoma/classification
• Small Cell Lung Carcinoma/metabolism
• Small Cell Lung Carcinoma/pathology

• adenoma
• biomarker
• blood
• colorectal cancer
• diagnosis
• feces
• miRNA
• prediction
• prognosis

• Adenomatous Polyps/genetics
• Biomarkers, Tumor
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/therapy
• Early Detection of Cancer
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/genetics
• Neoplasm Metastasis
• Neoplasm Staging
• Prognosis
• Treatment Outcome

• R01 CA72851 NCI NIH HHS
• CA181572 NCI NIH HHS
• R01 CA184792 NCI NIH HHS
• CA184792 NCI NIH HHS
• R01 CA181572 NCI NIH HHS
• R01 CA072851 NCI NIH HHS

MicroRNAs (miRNAs) offer great potential as cancer biomarkers. The importance of miRNAs profiling in tissue and body fluids in colorectal cancer (CRC) have been addressed respectively in many studies. The purpose of our study is to systematically assess the expression of miRNAs in cancer tissue and matched plasma samples and to evaluate their usefulness as minimally invasive diagnostic biomarkers for the detection of CRC.

The study was divided into two phases: firstly, qRT-PCR based TaqMan Low Density MiRNA Arrays (TLDAs) was used to screen the differentially expressed miRNAs in 6 plasma samples of CRC patients and 6 healthy controls. Secondly, marker validation by stem-loop reverse transcription real-time PCR using an independent set of paired cancer tissues (n = 88) and matched plasma samples (CRC, n = 88; control, n = 40). Correlation analysis was determined by Pearson’s test. Receiver operating characteristic curve analyses were applied to obtain diagnostic utility of the differentially expressed miRNAs. Target gene prediction and signal pathway analyses were used to predict the function of miRNAs.

TLDAs identified 42 miRNAs, which were differentially expressed in patients and healthy individuals. Five of them (miR-375, miR-150, miR-206, miR-125b and miR-126*) were chosen to be validated in plasma and tissue samples. The results indicated that for plasma sample, miR-375 (p < 0.0001) and miR-206 (p = 0.0002) were dysregulated and could discriminate CRC patients from healthy controls. For tissue samples, miR-375 (p < 0.0001), miR-150 (p < 0.0001), miR-125b (p = 0.0065) and miR-126*(p = 0.0009) were down-regulated. miR-375 was significantly down-regulated and positively correlated in both tissue and plasma samples (r = 0.4663, p = 0.0007). Gene ontology and signal pathway analyses showed that most of the target genes that were regulated by miR-375 were involved in some critical pathways in the development and progression of cancer.

Our results indicate that the down-regulation of miR-375 in plasma and tissue is matched in CRC. Moreover, bioinformatics prediction revealed miR-375 association with some critical signal pathways in the development and progression of CRC. Therefore, plasma miR-375 holds great promise to be an alternative tissue biomarker for CRC detection.

The online version of this article (doi:10.1186/1471-2407-14-714) contains supplementary material, which is available to authorized users.

• AEG-1/MTDH/LYRIC
• Chemoresistance
• NFκB
• SND1
• miR-375

• mirna
• diabetic nephropathy
• biomarkers

• Biomarkers/urine
• Diabetic Nephropathies/physiopathology
• Diabetic Nephropathies/urine
• Humans
• MicroRNAs/urine

• R01 DK060635 NIDDK NIH HHS

AIM: To investigate the regulative effect of miRNA-338-3p (miR-338-3p) on cell growth in colorectal carcinoma (CRC).

METHODS: The lentiviral vector pLV-THM-miR-338-3p and pLV-THM-miR-338-3p-inhibitor were constructed. The recombinant viral vector encoding the pre-miR-338-3p or miR-338-3p-inhibitor and the two packaging plasmids psPAX2 and pMD2.G were cotransfected into human embryonic kidney 293T cells to package lentivirus. The supernatant containing the lentivirus particles was harvested to determine the viral titer, and this supernatant was then used to transduce CRC-derived cell line, SW-620. Flow cytometry was utilized for sorting the green fluorescent protein (GFP)⁺ cells to establish the SW-620 cell line stably expressing pre-miR-338-3p or miR-338-3p-inhibitor. Moreover, the expression of miR-338-3p was determined by real-time reverse transcriptase polymerase chain reaction, and Western blotting was used to detect the expression of the smoothened (SMO, the possible target of miR-338-3p) protein in SW-620 cells. Furthermore, the status of CRC cell proliferation and apoptosis were detected by 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay and flow cytometry, respectively.

RESULTS: Restriction enzyme digestion and DNA sequencing demonstrated that the lentiviral vector pLV-THM-miR-338-3p and pLV-THM-miR-338-3p-inhibitor were constructed successfully. GFP was expressed after the SW-620 cells were transduced by the lentivirus. Expression of miR-338-3p in SW-620 cells transduced with the lentivirus pLV-THM-miR-338-3p was significantly increased (relative expression 3.91 ± 0.51 vs 2.36 ± 0.44, P < 0.01). Furthermore, overexpression of miR-338-3p inhibited the expression of SMO protein in SW-620 cells, which showed obviously suppressed proliferation ability [cellular proliferation inhibition rate (CPIR) 61.9% ± 5.2% vs 41.6% ± 4.8%, P < 0.01]. Expression of miR-338-3p in SW-620 cells transduced with the lentivirus pLV-THM-miR-338-3p-inhibitor was significantly decreased (relative expression 0.92 ± 0.29 vs 2.36 ± 0.44, P < 0.01). Moreover, the downregulated expression of miR-338-3p caused upregulated expression of the SMO protein in SW-620 cells, which showed significantly enhanced proliferation ability (CPIR 19.2% ± 3.8% vs 41.6% ± 4.8%, P < 0.01). However, anti-SMO-siRNA largely, but not completely, reversed the effects induced by blockage of miR-338-3p, suggesting that the regulative effect of miR-338-3p on CRC cell growth was indeed mediated by SMO.

CONCLUSION: miR-338-3p could suppress CRC growth by inhibiting SMO protein expression.

• Colorectal carcinoma
• Hsa-miRNA-338-3p
• Smoothened
• Lentivirus

• Apoptosis
• Cell Line, Tumor
• Cell Proliferation
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/pathology
• Genetic Vectors
• HEK293 Cells
• Humans
• Lentivirus/genetics
• MicroRNAs/metabolism
• RNA Interference
• Receptors, G-Protein-Coupled/genetics
• Receptors, G-Protein-Coupled/metabolism
• Signal Transduction
• Smoothened Receptor
• Transduction, Genetic
• Transfection
• Up-Regulation

• miR-375
• microRNA
• pancreatic cancer

The discovery of microRNA, a group of regulatory short RNA fragments, has added a new dimension to the diagnosis and management of neoplastic diseases. Differential expression of microRNA in a unique pattern in a wide range of tumor types enables researches to develop a microRNA-based assay for source identification of metastatic disease of unknown origin. This is just one example of many microRNA-based cancer diagnostic and prognostic assays in various phases of clinical research.

Since colorectal cancer (CRC) is a phenotypic expression of multiple molecular pathways including chromosomal instability (CIN), micro-satellite instability (MIS) and CpG islands promoter hypermethylation (CIMP), there is no one-unique pattern of microRNA expression expected in this disease and indeed, there are multiple reports published, describing different patterns of microRNA expression in CRC.

The scope of this manuscript is to provide a comprehensive review of the scientific literature describing the dysregulation of and the potential role for microRNA in the management of CRC. A Pubmed search was conducted using the following MeSH terms, "microRNA" and "colorectal cancer". Of the 493 publications screened, there were 57 papers describing dysregulation of microRNA in CRC.

• colorectal cancer
• microRNA

Although lymph node negative (LN-) breast cancer patients have a good 10-years survival (∼85%), most of them still receive adjuvant therapy, while only some benefit from this. More accurate prognostication of LN- breast cancer patient may reduce over- and under-treatment. Until now proliferation is the strongest prognostic factor for LN- breast cancer patients. The small molecule microRNA (miRNA) has opened a new window for prognostic markers, therapeutic targets and/or therapeutic components. Previously it has been shown that miR-18a/b, miR-25, miR-29c and miR-106b correlate to high proliferation.

The current study validates nine miRNAs (miR-18a/b miR-25, miR-29c, miR-106b, miR375, miR-424, miR-505 and let-7b) significantly correlated with established prognostic breast cancer biomarkers. Total RNA was isolated from 204 formaldehyde-fixed paraffin embedded (FFPE) LN- breast cancers and analyzed with quantitative real-time Polymerase Chain Reaction (qPCR). Independent T-test was used to detect significant correlation between miRNA expression level and the different clinicopathological features for breast cancer.

Strong and significant associations were observed for high expression of miR-18a/b, miR-106b, miR-25 and miR-505 to high proliferation, oestrogen receptor negativity and cytokeratin 5/6 positivity. High expression of let-7b, miR-29c and miR-375 was detected in more differentiated tumours. Kaplan-Meier survival analysis showed that patients with high miR-106b expression had an 81% survival rate vs. 95% (P = 0.004) for patients with low expression.

High expression of miR-18a/b are strongly associated with basal-like breast cancer features, while miR-106b can identify a group with higher risk for developing distant metastases in the subgroup of Her2 negatives. Furthermore miR-106b can identify a group of patients with 100% survival within the otherwise considered high risk group of patients with high proliferation. Using miR-106b as a biomarker in conjunction to mitotic activity index could thereby possibly save 18% of the patients with high proliferation from overtreatment.

• Adult
• Aged
• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/genetics
• Breast Neoplasms/diagnosis
• Breast Neoplasms/genetics
• Breast Neoplasms/pathology
• Cell Proliferation
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Kaplan-Meier Estimate
• Lymph Nodes/pathology
• MicroRNAs/analysis
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Middle Aged
• Prognosis
• Receptors, Estrogen/metabolism
• Survival Rate