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MicroRNAs and triple negative breast cancer.

ABSTRACT: Triple Negative Breast Cancer (TNBC) is a very aggressive tumor subtype, which still lacks specific markers for an effective targeted therapy. Despite the common feature of negativity for the three most relevant receptors (ER, PgR and HER2), TNBC is a very heterogeneous disease where different subgroups can be recognized, and both gene and microRNA profiling studies have recently been carried out to dissect the different molecular entities. Moreover, several microRNAs playing a crucial role in triple negative breast cancer biology have been identified, providing the experimental basis for a possible therapeutic application. Indeed, the causal involvement of microRNAs in breast cancer and the possible use of these small noncoding RNA molecules as biomarkers has been extensively studied with promising results. Their application as therapeutic tools might represent an innovative approach, especially for a tumor subgroup still lacking an efficient and specific therapy such as TNBC. In this review, we summarize our knowledge on the most important microRNAs described in TNBC.

SUBMITTER: D'Ippolito E

PROVIDER: S-EPMC3856060 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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MicroRNAs and triple negative breast cancer.

D'Ippolito Elvira E Iorio Marilena V MV

International journal of molecular sciences 20131111 11

Triple Negative Breast Cancer (TNBC) is a very aggressive tumor subtype, which still lacks specific markers for an effective targeted therapy. Despite the common feature of negativity for the three most relevant receptors (ER, PgR and HER2), TNBC is a very heterogeneous disease where different subgroups can be recognized, and both gene and microRNA profiling studies have recently been carried out to dissect the different molecular entities. Moreover, several microRNAs playing a crucial role in t ...[more]

PMID: 24284394

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Project description:BackgroundMicroRNAs (miRNAs) are short, non-coding RNA molecules that play critical roles in human malignancy. However, the regulatory characteristics of miRNAs in triple-negative breast cancer, a phenotype of breast cancer that does not express the genes for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, are still poorly understood.MethodsIn this study, miRNA expression profiles of 24 triple-negative breast cancers and 14 adjacent normal tissues were analyzed using deep sequencing technology. Expression levels of miRNA reads were normalized with the quantile-quantile scaling method. Deregulated miRNAs in triple-negative breast cancer were identified from the sequencing data using the Student's t-test. Quantitative reverse transcription PCR validations were carried out to examine miRNA expression levels. Potential target candidates of a miRNA were predicted using published target prediction algorithms. Luciferase reporter assay experiments were performed to verify a putative miRNA-target relationship. Validated molecular targets of the deregulated miRNAs were retrieved from curated databases and their associations with cancer progression were discussed.ResultsA novel 25-miRNA expression signature was found to effectively distinguish triple-negative breast cancers from surrounding normal tissues in a hierarchical clustering analysis. We documented the evidence of seven polycistronic miRNA clusters preferentially harboring deregulated miRNAs in triple-negative breast cancer. Two of these miRNA clusters (miR-143-145 at 5q32 and miR-497-195 at 17p13.1) were markedly down-regulated in triple-negative breast cancer, while the other five miRNA clusters (miR-17-92 at 13q31.3, miR-183-182 at 7q32.2, miR-200-429 at 1p36.33, miR-301b-130b at 22q11.21, and miR-532-502 at Xp11.23) were up-regulated in triple-negative breast cancer. Moreover, miR-130b-5p from the miR-301b-130b cluster was shown to directly repress the cyclin G2 (CCNG2) gene, a crucial cell cycle regulator, in triple-negative breast cancer cells. Luciferase reporter assays showed that miR-130b-5p-mediated repression of CCNG2 was dependent on the sequence of the 3'-untranslated region. The findings described in this study implicate a miR-130b-5p-CCNG2 axis that may be involved in the malignant progression of triple-negative breast cancer.ConclusionsOur work delivers a clear picture of the global miRNA regulatory characteristics in triple-negative breast cancer and extends the current knowledge of microRNA regulatory network.

Project description:Breast cancer (BC) is the most common type of cancer in women worldwide, and despite advances in treatments, its incidence and mortality are increasing. Therefore, it is necessary to develop new, non-invasive tests that provide more accurate diagnosis and prognosis in a timely manner. A promising approach is measuring the presence of biomarkers to detect tumors at various stages and determine their specific characteristics, thus allowing for more personalized treatment. MicroRNAs (miRNAs) serve a role in gene expression, primarily by interacting with messenger RNAs, and may be potential biomarkers for detecting cancer. They are detectable in tissues and blood, including plasma and/or serum, are stable and often tumor specific. Also, different miRNAs are associated with specific BC molecular subtypes. Triple-negative BC (TNBC) is a type of BC in which the primary targets for hormonal therapy are absent. It is an aggressive phenotype, which frequently metastasizes and is associated with an unfavorable prognosis. The present review focuses on circulating miRNAs in patients with TNBC, with an emphasis on their interaction with the immune response checkpoint genes PD-1, PD-L1 and CTLA4. Modulation and response of the immune system are of interest in cancer treatment due to the success of immunotherapy in the treatment of various neoplasms. Based on the findings of this literature review and the in silico analysis performed as part of this review, it is concluded that circulating hsa-miR-195 and hsa-miR-155 in TNBC interact with checkpoint genes involved in the immune response. Further analysis of the expression of these circulating miRNAs and their association with prognosis in patients with TNBC treated with immunotherapy should be assessed to evaluate their possible use as non-invasive predictive biomarkers. In addition, functional studies to analyze biologically relevant targets in the development and prognosis of TNBC, which could be therapeutic targets, are also recommended.

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MicroRNAs and triple negative breast cancer.

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MicroRNAs and triple negative breast cancer.

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