Micro-RNAs and breast cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Le Quesne J
PROVIDER: S-EPMC5527936 | biostudies-other | 2010 Jun
REPOSITORIES: biostudies-other
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Project description:Micro (mi)RNAs are an endogenous non-coding small RNA comprised of 19-26 nucleotides. miRNAs regulate gene expression through the recognition of its 'seed sequence' and interactions with 3'-untranslated region of target miRNAs. Previous studies identified that miRNAs are associated with the onset and development of breast cancer and that a number of mutations in the coding DNA sequence of miRNAs affect its expression. Therefore, the present study aimed to screen differentially expressed miRNAs using miRNA expression profile chips to analyze the expression of miRNA (miR)-205 in 12 breast cell lines of different metastatic performance and benign proliferative variation as well as breast cancer via in-situ hybridization, and screen out single-nucleotide polymorphisms (SNPs) in the miR-205 coding gene region. In addition, the association between SNP and the clinicopathological features of breast lesions was investigated. The results of the present study demonstrated that the expression of miR-205 was decreased in breast cancer cells and tissues compared with benign lesions. SNPs in the miR-205 coding gene region were identified in tumor cell lines and as increasing lengths of the AGC repetitive sequence were lost, miR-205 expression increased. An association was identified between a number of SNPs in the miR-205 coding gene region and breast cancer, as well as between SNPs in miR-205 coding gene region and the clinicopathological features of breast cancer.
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Project description:Breast cancer (BC) is the most frequent type of non skin cancer among women and a major leading cause of cancer-related deaths in Western countries. It is substantial to discover novel biomarkers with diagnostic, prognostic or predictive usefulness as well as therapeutic value for BC. Micro-RNAs (miRNAs) belong to a novel class of endogenous interfering RNAs that play a crucial role in post transcriptional gene silencing through mRNA targeting and, thus, are involved in many biological processes encompassing apoptosis, cell-cycle control, cell proliferation, DNA repair, immunity, metabolism, stress, aging, etc. MiRNAs exert their action mainly in a tumor suppressive or oncogenic manner. The specific aberrant expression patterns of miRNAs in BC that are detected with the use of high-throughput technologies reflect their key role in cancer initiation, progression, migration, invasion and metastasis. The detection of circulating extracellular miRNAs in plasma of BC patients may provide novel, non-invasive biomarkers in favor of BC diagnosis and prognosis and, at the same time, accumulating evidence has underscored the possible contribution of miRNAs as valuable biomarkers to predict response to chemotherapy or radiotherapy. Data from in vitro and in vivo studies on BC have revealed promising therapeutic approaches via miRNA delivery and miRNA inhibition. The purpose of this review is to explore the ontological role of miRNAs in BC etiopathogenesis as well as to highlight their potential, not only as non-invasive circulating biomarkers with diagnostic and prognostic significance, but also as treatment response predictors and therapeutic targets aiding BC management.
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Project description:INTRODUCTION: MicroRNAs (miRNAs, miRs) are a class of small, non-coding RNA molecules with relevance as regulators of gene expression thereby affecting crucial processes in cancer development. MiRNAs offer great potential as biomarkers for cancer detection due to their remarkable stability in blood and their characteristic expression in many different diseases. We investigated whether microarray-based miRNA profiling on whole blood could discriminate between early stage breast cancer patients and healthy controls. METHODS: We performed microarray-based miRNA profiling on whole blood of 48 early stage breast cancer patients at diagnosis along with 57 healthy individuals as controls. This was followed by a real-time semi-quantitative Polymerase Chain Reaction (RT-qPCR) validation in a separate cohort of 24 early stage breast cancer patients from a breast cancer screening unit and 24 age matched controls using two differentially expressed miRNAs (miR-202, miR-718). RESULTS: Using the significance level of p<0.05, we found that 59 miRNAs were differentially expressed in whole blood of early stage breast cancer patients compared to healthy controls. 13 significantly up-regulated miRNAs and 46 significantly down-regulated miRNAs in our microarray panel of 1100 miRNAs and miRNA star sequences could be detected. A set of 240 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 78.8%, and a sensitivity of 92.5%, as well as an accuracy of 85.6%. Two miRNAs were validated by RT-qPCR in an independent cohort. The relative fold changes of the RT-qPCR validation were in line with the microarray data for both miRNAs, and statistically significant differences in miRNA-expression were found for miR-202. CONCLUSIONS: MiRNA profiling in whole blood has potential as a novel method for early stage breast cancer detection, but there are still challenges that need to be addressed to establish these new biomarkers in clinical use.
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