• Cancer
• HIF signalling
• MiR-210
• MicroRNA
• Tumorigenesis

• Humans
• MicroRNAs/metabolism
• Signal Transduction/genetics
• Neoplasms/genetics
• Hypoxia
• Cell Hypoxia
• Carcinogenesis/genetics
• Hypoxia-Inducible Factor 1, alpha Subunit/genetics
• Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic/genetics
• Tumor Microenvironment/genetics

• HIFs
• breast cancer
• circRNAs
• hypoxia
• lncRNAs
• miRNAs
• ncRNA

• Bcl-2
• Beclin-1
• Hypoxia-inducible factor-1α (HIF-1α)
• Triple-negative breast cancer (TNBC)
• miR-210

• HIF1-alpha
• anaplastic thyroid cancer
• extracellular vesicles
• hypoxia
• miR-210
• miRNA
• microRNA

• Humans
• Cell Line, Tumor
• Extracellular Vesicles/metabolism
• Gene Expression Regulation, Neoplastic
• Hypoxia/genetics
• MicroRNAs/genetics
• Oxygen/metabolism
• Thyroid Carcinoma, Anaplastic/pathology
• Thyroid Neoplasms/metabolism
• Argonaute Proteins

• UH3 CA241694 NCI NIH HHS

• BRCA1
• BRCA2
• biomarker
• familial breast cancer
• prognostic and predictive

• TNBC
• biomarkers
• meta-analysis
• miRNA
• prognosis
• systematic review

Breast cancer is a kind of malignant tumor disease that poses a serious threat to human health. Its biological characteristics of rapid proliferation and delayed angiogenesis, lead to intratumoral hypoxia as a common finding in breast cancer. HIF as a transcription factor, mediate a series of reactions in the hypoxic microenvironment, including metabolic reprogramming, tumor angiogenesis, tumor cell proliferation and metastasis and other important physiological and pathological processes, as well as gene instability under hypoxia. In addition, in the immune microenvironment of hypoxia, both innate and acquired immunity of tumor cells undergo subtle changes to support tumor and inhibit immune activity. Thus, the elucidation of tumor microenvironment hypoxia provides a promising target for the resistance and limited efficacy of current breast cancer therapies. We also summarize the hypoxic mechanisms of breast cancer treatment related drug resistance, as well as the current status and prospects of latest related drugs targeted HIF inhibitors.

Nav1.5 is one of the nine voltage-gated sodium channel-alpha subunit (VGSC-α) family members. The Nav1.5 channel typically carries an inward sodium ion current that depolarises the membrane potential during the upstroke of the cardiac action potential. The neonatal isoform of Nav1.5, nNav1.5, is produced via VGSC-α alternative splicing. nNav1.5 is known to potentiate breast cancer metastasis. Despite their well-known biological functions, the immunological perspectives of these channels are poorly explored. The current review has attempted to summarise the triad between Nav1.5 (nNav1.5), breast cancer, and the immune system. To date, there is no such review available that encompasses these three components as most reviews focus on the molecular and pharmacological prospects of Nav1.5. This review is divided into three major subsections: (1) the review highlights the roles of Nav1.5 and nNav1.5 in potentiating the progression of breast cancer, (2) focuses on the general connection between breast cancer and the immune system, and finally (3) the review emphasises the involvements of Nav1.5 and nNav1.5 in the functionality of the immune system and the immunogenicity. Compared to the other subsections, section three is pretty unexploited; it would be interesting to study this subsection as it completes the triad.

N6-methyladenosine(m6A) methylation modification affects the tumorigenesis, progression, and metastasis of breast cancer (BC). However, the expression characteristics and prognostic value of m6A modification in BC are still unclear. We aimed to evaluate the relationship between m6A modification and clinicopathological characteristics, and to explore the underlying mechanisms.

Three public cohorts and our clinical cohort were included: 1091 BC samples and 113 normal samples from the TCGA database, 1985 BC samples from the METABRIC database, 1764 BC samples from the KM Plotter website, and 134 BC samples of our clinical cohort. We collected date from these cohorts and analyzed the genetic expression, gene-gene interactions, gene mutations, copy number variations (CNVs), and clinicopathological and prognostic features of 28 m6A RNA regulators in BC.

This study demonstrated that some m6A regulators were significantly differenially expressed in BCs and their adjacent tissues, and also different in various molecular types. All 28 studied m6A regulators exhibited interactions. KIAA1429 had the highest mutation frequency. CNVs of m6A regulators were observed in BC patients. The expression of the m6A regulators was differentially associated with survival of BC. Higher CBLL1 expression was associated with a better prognosis in BC than lower CBLL1 expression. Functional analysis showed that CBLL1 was related to the ESR1-related pathway, apoptosis-related pathway, cell cycle pathway and immune-related pathway in BC.

m6A RNA modification modulated gene expression and thereby affected clinicopathological features and survival outcomes in BC. CBLL1 may be a promising prognostic biomarker for BC patients.

The online version contains supplementary material available at 10.1186/s40364-021-00285-w.

• Breast cancer
• CBLL1
• Methylation
• N6-methyladenosine modification
• Prognosis

• chemoresistance
• circulating miRNA
• theranostic markers
• triple-negative breast cancer

• Adult
• Biomarkers, Tumor/blood
• Biomarkers, Tumor/genetics
• Case-Control Studies
• Circulating MicroRNA/genetics
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Humans
• Pharmaceutical Preparations/administration & dosage
• Prognosis
• Survival Rate
• Triple Negative Breast Neoplasms/blood
• Triple Negative Breast Neoplasms/drug therapy
• Triple Negative Breast Neoplasms/genetics
• Triple Negative Breast Neoplasms/pathology

• Breast cancer
• Cell migration
• Cell proliferation
• MiRNA-mRNA interaction
• miR-193
• miR-210

• Cancer epigenetics
• Chemoprevention
• EGCG
• Epigenetic regulator
• Green tea polyphenols

• Biomarker
• Genotoxicity
• Mutagen
• miR-34a
• miRNA expression

• DEPTOR
• breast cancer
• cell proliferation
• miR-671-3p
• neoplasm invasiveness

Hypoxia is a classic characteristic of the tumor microenvironment with a significant impact on cancer progression and therapeutic response. Hypoxia-inducible factor-1 alpha (HIF-1α), the most important transcriptional regulator in the response to hypoxia, has been demonstrated to significantly modulate hypoxic gene expression and signaling transduction networks. In past few decades, growing numbers of studies have revealed the importance of noncoding RNAs (ncRNAs) in hypoxic tumor regions. These hypoxia-responsive ncRNAs (HRNs) play pivotal roles in regulating hypoxic gene expression at the transcriptional, posttranscriptional, translational and posttranslational levels. In addition, as a significant gene expression regulator, ncRNAs exhibit promising roles in regulating HIF-1α expression at multiple levels. In this review, we briefly elucidate the reciprocal regulation between HIF-1α and ncRNAs, as well as their effect on cancer cell behaviors. We also try to summarize the complex feedback loop existing between these two components. Moreover, we evaluated the biomarker potential of HRNs for the diagnosis and prognosis of cancer, as well as the potential clinical utility of shared regulatory mechanisms between HIF-1α and ncRNAs in cancer treatment, providing novel insights into tumorigenicity, which may lead to innovative clinical applications.

• HIF-1α
• carcinogenesis
• clinical practice
• ncRNA

• Pancreatic cancer cells
• hypoxia
• hypoxia-inducible factor-1α
• miR-210
• nuclear factor κB

• biomarkers
• breast cancer
• microRNAs
• prognosis

• Diagnosis
• microRNA
• prognosis
• treatment
• triple-negative breast cancer

• Breast cancer
• FOXA2
• MicroRNA-942
• Prognosis
• Progression

• Apoptosis/genetics
• Breast Neoplasms/genetics
• Cadherins/genetics
• Case-Control Studies
• Cell Line, Tumor
• Cell Movement/genetics
• Cell Proliferation/genetics
• Cell Survival/genetics
• Cells, Cultured
• Down-Regulation/genetics
• Female
• Gene Expression Regulation, Neoplastic/genetics
• Hepatocyte Nuclear Factor 3-beta/genetics
• Humans
• MCF-7 Cells
• MicroRNAs/genetics
• Prognosis
• Up-Regulation/genetics

Triple-negative breast cancer (TNBC) is the most aggressive, prevalent, and distinct subtype of breast cancer characterized by high recurrence rates and poor clinical prognosis, devoid of both predictive markers and potential therapeutic targets. MicroRNAs (miRNA/miR) are a family of small, endogenous, non-coding, single-stranded regulatory RNAs that bind to the 3′-untranslated region (3′-UTR) complementary sequences and downregulate the translation of target mRNAs as post-transcriptional regulators. Dysregulation miRNAs are involved in broad spectrum cellular processes of TNBC, exerting their function as oncogenes or tumor suppressors depending on their cellular target involved in tumor initiation, promotion, malignant conversion, and metastasis. In this review, we emphasize on masses of miRNAs that act as oncogenes or tumor suppressors involved in epithelial–mesenchymal transition (EMT), maintenance of stemness, tumor invasion and metastasis, cell proliferation, and apoptosis. We also discuss miRNAs as the targets or as the regulators of dysregulation epigenetic modulation in the carcinogenesis process of TNBC. Furthermore, we show that miRNAs used as potential classification, prognostic, chemotherapy and radiotherapy resistance markers in TNBC. Finally, we present the perspective on miRNA therapeutics with mimics or antagonists, and focus on the challenges of miRNA therapy. This study offers an insight into the role of miRNA in pathology progression of TNBC.

• chemotherapy and radiotherapy resistance
• epigenetic mechanisms
• miRNAs
• prognosis
• therapeutic strategies
• triple-negative breast cancer (TNBC)
• tumorigenesis

• Biomarkers, Tumor/genetics
• Carcinogenesis/genetics
• Drug Resistance, Neoplasm/genetics
• Humans
• MicroRNAs/genetics
• Triple Negative Breast Neoplasms/diagnosis
• Triple Negative Breast Neoplasms/genetics
• Triple Negative Breast Neoplasms/pathology
• Triple Negative Breast Neoplasms/therapy

• biomarker
• cancer
• diagnosis
• microRNAs
• prognosis
• signal pathway

• copy number
• disparities
• latinas
• microRNA
• triple-negative breast cancer

• P30 CA051008 NCI NIH HHS
• U01 FD004319 FDA HHS

MicroRNA-210-3p is the most prominent hypoxia regulated microRNA, and it has been found significantly overexpressed in different human cancers. We performed the expression analysis of miR-210-3p in a retrospective cohort of breast cancer patients with a median follow-up of 76 months (n = 283). An association between higher levels of miR-210-3p and risk of disease progression (HR: 2.13, 95%CI: 1.33-3.39, P = 0.002) was found in the subgroup of patients treated with Epirubicin and Cyclophosphamide followed by Docetaxel. Moreover, a cut off value of 20.966 established by ROC curve analyses allowed to discriminate patients who developed distant metastases with an accuracy of 85% at 3- (AUC: 0.870, 95%CI: 0.690-1.000) and 83% at 5-years follow up (AUC: 0.832, 95%CI: 0.656–1.000). Whereas the accuracy in discriminating patients who died for the disease was of 79.6% at both 5- (AUC: 0.804, 95%CI: 0.517–1.000) and 10-years (AUC: 0.804. 95%CI: 0.517–1.000) follow-up. In silico analysis of miR-210-3p and Docetaxel targets provided evidence for a putative molecular cross-talk involving microtubule regulation, drug efflux metabolism and oxidative stress response. Overall, our data point to the miR-210-3p involvement in the response to therapeutic regimens including Docetaxel in sequential therapy with anthracyclines, suggesting it may represent a predictive biomarker in breast cancer patients.

Background: MicroRNAs contribute to chemotherapy response in different types of cancer. We hypothesized that plasma miRNAs are potentially associated with chemotherapy response in patients with metastatic breast cancer. Patients and Methods: Fourteen candidate microRNAs were chosen from the literature, and their plasma levels were measured by quantitative polymerase chain reaction (PCR). Forty metastatic breast cancer patients were chosen as the training groups. The potential significant microRNAs were validated in another 103 plasma samples. Results: In the training set, we identified 3 microRNAs (miR-200a, miR-210, and miR-451) as significantly dysregulated miRNAs between sensitive group (partial response (and stable disease) and resistant group (progressive disease). Then, in the validation set, miR-200a (area under the curve = 0.881, sensitivity = 94.1%, specificity = 76.7%) and miR-210 (area under the curve = 0.851, sensitivity = 88.2%, specificity = 72.1%) showed high diagnostic accuracy for distinguishing sensitive group from resistant group. Furthermore, the plasma level of miR-200a was significantly associated with the stage in surgery (P = .035), and the high level of miR-210 expression was associated with internal organ metastasis (liver, lung, and brain; P = .024). Conclusions: Plasma miR-200a and miR-210 could be effective biomarkers for the prediction of chemotherapy resistance in metastatic breast cancer patients.

• chemoresistance
• metastatic breast cancer
• miRNA
• plasma
• predictive

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’.

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.

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.

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.

The online version of this article (10.1186/s13046-018-0920-2) contains supplementary material, which is available to authorized users.

• Double positive breast cancer
• Plasma miRNA
• Triple negative breast cancer

• biomarkers
• next-generation sequencing
• overall survival
• relapse-free survival
• treatment response

Triple Negative Breast Cancer (TNBC), a clinically aggressive subtype of breast cancer, disproportionately affects African American (AA) women when compared to non-Hispanic Whites (NHW). MiRNAs(miRNAs) play a critical role in these tumors, through the regulation of cancer driver genes. In this study, our goal was to characterize and compare the patterns of miRNA expression in TNBC of AA (n = 27) and NHW women (n = 30). A total of 256 miRNAs were differentially expressed between these groups, and distinct from the ones observed in their respective non-TNBC subtypes. Fifty-five of these miRNAs were mapped in cytobands carrying copy number alterations (CNAs); 26 of them presented expression levels concordant with the observed CNAs. Receiving operating characteristic (ROC) analysis showed a good power (AUC ≥ 0.80; 95% CI) for over 65% of the individual miRNAs and a high combined power with superior sensitivity and specificity (AUC = 0.88 (0.78−0.99); 95% CI) of the 26 miRNA panel in discriminating TNBC between these populations. Subsequent miRNA target analysis revealed their involvement in the interconnected PI3K/AKT, MAPK and insulin signaling pathways. Additionally, three miRNAs of this panel were associated with early age at diagnosis. Altogether, these findings indicated that there are different patterns of miRNA expression between TNBC of AA and NHW women and that their mapping in genomic regions with high levels of CNAs is not merely physical, but biologically relevant to the TNBC phenotype. Once validated in distinct cohorts of AA women, this panel can potentially represent their intrinsic TNBC genome signature.

• African American
• copy number
• microRNA
• non-Hispanic white
• triple negative breast cancer

Female breast cancer is frequently diagnosed at a later stage and the leading cause of cancer deaths world-wide. Levels of cell-free circulating microRNAs (miRNAs) can potentially be used as biomarkers to measure disease progression in breast cancer patients in a non-invasive way and are therefore of high clinical value.

Using quantitative RT-PCR, circulating miRNAs were measured in blood samples collected from disease-free individuals (n = 34), triple-negative breast tumours (TNBC) (n = 36) and luminal tumours (n = 57). In addition to intergroup comparisons, plasma miRNA expression levels of all groups were analyzed against RNASeq data from cancerous breast tissue via The Cancer Genome Atlas (TCGA).

A differential set of 18 miRNAs were identified in the plasma of breast cancer patients and 10 miRNAs were uniquely identified based on ROC analysis. The most striking findings revealed elevated tumor suppressor let-7 miRNA in luminal breast cancer patients, irrespective of subtype, and elevated miR-195 in plasma of TNBC breast cancer patients. In contrast, hsa-miR-195 and let-7 miRNAs were absent from cancerous TCGA tissue and strongly expressed in surrounding non-tumor tissue indicating that cancerous cells may selectively export tumor suppressor hsa-miR-195 and let-7 miRNAs in order to maintain oncogenesis.

While studies have indicated that the restoration of let-7 and miR-195 may be a potential therapy for cancer, these results suggested that tumor cells may selectively export hsa-miR-195 and let-7 miRNAs thereby neutralizing their potential therapeutic effect. However, in order to facilitate earlier detection of breast cancer, blood based screening of hsa-miR-195 and let-7 may be beneficial in a female patient cohort.

The online version of this article (10.1186/s12885-017-3776-5) contains supplementary material, which is available to authorized users.

• Cancer therapy
• Circulating biomarkers
• Circulating miRNAs
• FASN pathway
• Plasma versus tissue
• ROC curves
• Secretion
• Triple-negative breast cancer (TNBC)

• cancer
• meta-analysis
• microrna-210
• prognosis

• Biomarkers, Tumor/metabolism
• Humans
• MicroRNAs/biosynthesis
• Neoplasms/metabolism
• Prognosis
• Up-Regulation

A number of studies have shown that noncoding RNAs (ncRNAs) are abnormally expressed in breast cancers. However, the roles of ncRNAs remain unclear in breast cancer. Here, we aim to investigate the potential diagnostic and prognostic roles of ncRNAs in breast cancer.

Comprehensive literature search in Medline and Web of Science and a meta-analysis were performed to identify the association between ncRNAs and diagnosis, prognosis, and clinicopathological features of breast cancer.

A total of 103 eligible studies, involving16, 828 independent participants, were included in the meta-analysis. In total, there were 98 individual and 11 grouped ncRNAs. 51 studies were eligible for survival analysis, 27 studies were eligible for diagnostic analysis, and 46 studies were eligible for clinicopathological features analysis. The abnormal expression of ncRNAs is associated with OS, RFS and PFS in breast cancer patients. For the diagnosis value of ncRNAs, the pooled OR and 95% CI for sensitivity, specificity, DOR and AUC on all ncRNAs were 0.83 [95% CI: 0.82- 0.84], 0.80 [95% CI: 0.79- 0.82], 24.77 [95% CI: 17.44- 35.16] and 0.9037, respectively. The analysis showed that downregulation of ncRNAs in breast cancer was associated with decreased risk of LNM, increased tumor size and PR expression, whereas, upregulation of ncRNAs was associated with increased HER2 expression.

High expression of ncRNAs was associated with poor OS, RFS, and PFS, while low expression of ncRNAs was related to favorable OS and RFS. Meanwhile, ncRNAs have potential diagnostic value for breast cancer.

• breast cancer
• diagnosis
• meta-analysis
• noncoding RNA
• prognosis

• biomarker
• meta-analysis
• microrna
• prognosis
• triple-negative breast cancer

• Biomarkers, Tumor/metabolism
• Humans
• MicroRNAs/metabolism
• Prognosis
• Triple Negative Breast Neoplasms/metabolism

• TNBC
• in situ hybridization
• miR-210
• tumor microenvironment

• Biomarker
• Diagnosis
• Early breast cancer
• Prognosis
• Therapy prediction
• microRNA

• breast cancer
• cancer stem cells
• circulating tumor cells
• omics
• personalized medicine
• predictive diagnostics
• prognosis
• stratification
• targeted therapy
• validated biomarker

Breast cancer affects approximately 12 % women worldwide and results in 14 % of all cancer-related fatalities. Breast cancer is commonly categorized into one of four main subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and basal), indicating molecular characteristics and informing treatment regimes. The most severe form of breast cancer is metastasis, when the tumour spreads from the breast tissue to other parts of the body. Significantly, the primary tumour subtype affects rates and sites of metastasis. Currently, up to 5 % of patients present with incurable metastasis, with an additional 10–15 % of patients going on to develop metastasis within 3 years of diagnosis. MicroRNAs (miRNAs) are short 21–25 long nucleotides that have been shown to significantly affect gene expression. Currently, >2000 miRNAs have been identified and significantly, specific miRNAs have been found associated with diseases states. Importantly, miRNAs are found circulating in the blood, presenting an opportunity to use these circulating disease-related miRNAs as biomarkers. Clearly, the identification of circulating miRNA specific to metastatic breast cancer presents a unique opportunity for early disease identification and for monitoring disease burden. Currently however, few groups have identified miRNA associated with metastatic breast cancer. Here, we review the literature surrounding the identification of metastatic miRNA in breast cancer patients, highlighting key areas where miRNA biomarker discovery could be beneficial, identifying key concepts, recognizing critical areas requiring further research and discussing potential problems.

Triple negative breast cancer (TNBC) is characterised by the lack of receptors for estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2). Since it cannot be treated by current endocrine therapies which target these receptors and due to its aggressive nature, it has one of the worst prognoses of all breast cancer subtypes. The only treatments remain chemo- and/or radio-therapy and surgery and because of this, novel biomarkers or treatment targets are urgently required to improve disease outcomes. MicroRNAs represent an attractive candidate for targeted therapies against TNBC, due to their natural ability to act as antisense interactors and regulators of entire gene sets involved in malignancy and their superiority over mRNA profiling to accurately classify disease. Here we review the current knowledge regarding miRNAs as biomarkers in TNBC and their potential use as therapeutic targets in this disease. Further, we review other epigenetic changes and interactions of these changes with microRNAs in this breast cancer subtype, which may lead to the discovery of new treatment targets for TNBC.

• DNA methylation
• microRNA
• triple negative breast cancer

• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Breast Neoplasms/genetics
• Breast Neoplasms/metabolism
• Breast Neoplasms/mortality
• Disease-Free Survival
• Female
• Gene Expression
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Prognosis
• Proportional Hazards Models

Increasing evidence indicates that most of the tumors are sustained by a distinct population of cancer stem cells (CSCs), which are responsible for growth, metastasis, invasion, and recurrence. CSCs are typically characterized by self-renewal, the key biological process allowing continuous tumor proliferation, as well as by differentiation potential, which leads to the formation of the bulk of the tumor mass. CSCs have several advantages over the differentiated cancer cell populations, including the resistance to radio- and chemotherapy, and their gene-expression programs have been shown to correlate with poor clinical outcome, further supporting the relevance of stemness properties in cancer. The observation that CSCs possess enhanced mechanisms of protection from reactive oxygen species (ROS) induced stress and a different metabolism from the differentiated part of the tumor has paved the way to develop drugs targeting CSC specific signaling. In this review, we describe the role of ROS and of ROS-related microRNAs in the establishment and maintenance of self-renewal and differentiation capacities of CSCs.

• Cell fate
• MicroRNA
• Triple negative breast cancer

• Cell Hypoxia/physiology
• Drug Delivery Systems
• Epithelial-Mesenchymal Transition/genetics
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Models, Biological
• Neoplasm Invasiveness/prevention & control
• Neoplasm Metastasis/prevention & control
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/prevention & control

Breast cancer is a complex and heterogeneous disease. Signaling by estrogen receptor (ER), progesterone receptor (PR), and/or human EGF-like receptor 2 (HER2) is a main driver in the development and progression of a large majority of breast tumors. Molecular characterization of primary tumors has identified major subtypes that correlate with ER/PR/HER2 status, and also subgroup divisions that indicate other molecular and cellular features of the tumors. While some of these research findings have been incorporated into clinical practice, several challenges remain to improve breast cancer management and patient survival, for which the integration of novel biomarkers into current practice should be beneficial. microRNAs (miRNAs) are a class of short non-coding regulatory RNAs with an etiological contribution to breast carcinogenesis. miRNA-based diagnostic and therapeutic applications are rapidly emerging as novel potential approaches to manage and treat breast cancer. Rapid technological development enables specific and sensitive detection of individual miRNAs or the entire miRNome in tissues, blood, and other biological specimens from breast cancer patients. This review focuses on recent miRNA research and its potential to address unmet clinical needs and challenges. The four sections presented discuss miRNA findings in the context of the following clinical challenges: biomarkers for early detection; prognostic and predictive biomarkers for treatment decisions using targeted therapies against ER and HER2; diagnostic and prognostic biomarkers for subgrouping of triple-negative breast cancer, for which there are currently no targeted therapies; and biomarkers for monitoring and characterization of metastatic breast cancer. The review concludes with a critical analysis of the current state of miRNA breast cancer research and the need for further studies using large patient cohorts under well-controlled conditions before considering the clinical implementation of miRNA biomarkers.

• blood
• diagnostics FFPE tissues
• formalin-fixed paraffin-embedded tissues
• miR
• miRNA

Hereditary triple-negative breast cancer patients have better recurrence-free survival than triple-negative sporadic ones. High expression of some of the miRNAs is related to worse overall and disease-free survival of triple-negative breast cancer patients. The attempt to associate expression level of some miRNA in triple-negative hereditary and sporadic breast cancers to disease specific survival was performed in this study.

Study group was made of 18 triple-negative breast cancer patients harboring the BRCA1 gene mutations and 32 triple-negative sporadic breast cancer patients. Quantitative amount of mir-10b, mir-21, mir-29a, mir-31, and mir-214 by real-time PCR was assessed. The disease-specific survival in relation of high and low levels of some of the miRNAs was analyzed using Log-rank (Mantel-Cox) test.

MiR-214 showed significantly higher expression level in sporadic tissues than in hereditary ones (p = 0.0005). Triple-negative breast cancer patients with high level of miR-214 showed significantly worse disease-specific survival than patients with low level (p = 0.0314).

Our finding suggests that miR-214 possibly could be used as a potential prognostic biomarker for triple-negative breast cancer patients.

The online version of this article (doi:10.1186/s13053-015-0028-z) contains supplementary material, which is available to authorized users.

• Hereditary and sporadic breast cancers
• MiRNA expressionm
• Triple-negative subtype

AIM: To screen microRNAs (miRNAs) associated with metastasis of gastric cancer (GC) by miRNA microarray and to explore the possible role of miRNA-210 in GC metastasis by bioinformatics.

METHODS: GC cell lines with low (RF1) or high metastatic potential (RF48) were used for miRNA expression profiling using human miRNA microarray. Expression of miRNA-210 in 7 GC cell lines was detected by RT-PCR. MiRNA-210 targets were obtained using miRWalk, and functions of these targets in GC were predicted with David online.

RESULTS: Compared with RF1 cells, 21 and 15 miRNAs were up-regulated and down-regulated in RF48 cells, respectively. Expression of miRNA-210 was further validated by real-time quantitative RT-PCR in multiple GC cell lines with different metastatic potential, which showed that miRNA-210 was overexpressed in GC cell lines with high metastatic potential. Bioinformatics analysis suggested that miRNA-210 was related with tumorgenesis and metastasis.

CONCLUSION: Screening miRNAs associated with metastasis lays a foundation for identifying early diagnostic markers and new therapeutic targets for GC metastasis. Expression profile of miRNAs associated with metastasis was obtained by miRNA microarray; dysregulated expression of miRNA-210 may be related with GC metastasis, and may serve as an early diagnostic biomarker and new treatment target.

• Stomach neoplasms
• miRNA-210
• Micro-array analysis
• Neoplasm metastasis
• Computational biology