Integrated MicroRNA and mRNA Signatures Associated with Survival in Triple Negative Breast Cancer

Cascione, Luciano; Gasparini, Pierluigi; Lovat, Francesca; Carasi, Stefania; Pulvirenti, Alfredo; Ferro, Alfredo; Alder, Hansjüerg; He, Gang; Vecchione, Andrea; Croce, Carlo M.; Shapiro, Charles L.; Huebner, Kay

doi:10.1371/journal.pone.0055910

Cited by 166 publications

(166 citation statements)

References 49 publications

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“…however, miR-493, as analyzed by NanoString's nCounter human miRNA expression profiling, was downregulated in TNBCs vs. normal breast tissues (37). The role of miR-493-5p remains unclear in breast cancer cell lines and in breast cancer at present.…”

Section: Discussionmentioning

confidence: 97%

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

et al. 2016

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Abstract. Breast cancer is a leading cause of cancer-related mortality among women. Altered fucosylation was found to be closely associated with tumorigenesis and metastasis of breast cancer. MicroRNAs (miRNAs) are important regulators of cell proliferation and metastasis, and aberrant miRNA expression has been observed in breast cancer. The present study aimed to evaluate the level of fucosyltransferase IV (FUT4) and miR-493-5p in breast cancer and investigate their relationship. In the present study, we demonstrated the differential expressional profiles of FUT4 and miR-493-5p in 29 clinical breast cancer tissues, matched adjacent tissue samples and two breast carcinoma cell lines (MCF-7 and MDA-MB-231). Briefly, altered expression levels of FUT4 modified the invasive activities and tumorigenicity of the MCF-7 and MDA-MB-231 cells. Further study demonstrated that miR-493-5p plays a role as a suppressor in breast cancer cell invasion and tumorigenicity. Moreover, the expression levels of miR-493-5p were inversely proportional to those of FUT4 both at the mRNA and protein levels. Luciferase reporter assays confirmed that miR-493-5p bound to the 3'-untranslated (3'-UTR) region of FUT4, and inhibited the expression of FUT4 in breast cancer cells. Taken together, our data suggest that FUT4 may have a potential role in the treatment of breast cancer, as well as miR-493-5p is a novel regulator of invasiveness and tumorigenicity of breast cancer cells through targeting FUT4. The miR-493-5p/FUT4 pathway has therapeutic potential in breast cancer. IntroductionBreast cancer is the most common invasive cancer and the second cause of cancer-related death in women (1,2). Each year more than a half a million new cases of breast cancer are diagnosed in the US and Europe (3), and in China. Breast cancer is a very heterogeneous disease. Some patients are cured by the surgical removal of the primary tumor while other patients suffer from metastasis and progression of the disease, despite adjuvant therapy. Therefore, it is essential to develop effective and safer therapeutic modalities against breast cancer.Glycosylation is one of the important steps of protein post-translational modifications, and ~50% of proteins are glycosylated (4). Protein glycosylation plays a role in a variety of cellular biological functions, such as cell-cell and cell-substrate adhesion, membrane organization, cell immunogenicity and protein targeting (5). Specific changes in the glycosylation patterns of cell surface glycoprotein have been shown to enhance the metastatic potential of tumor cells. Aberrant expression of fucosylated glycans has also been detected in various types of tumors.The fucosyltransferase (FUT) family is a group of fucosylation synthases that catalyze the transfer of L-fucose (Fuc) from an activated GDP-β-L-Fuc to various acceptor molecules such as N-acetyllactosamine. The transfer of Fuc residue from the donor substrate, GDP-Fuc, is catalyzed to the oligosaccharide acceptor in a1, a1, FUT4, FUT5, FUT6, FUT7, FUT9, FUT10 and FUT1...

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Section: Discussionmentioning

confidence: 97%

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

et al. 2016

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“…Very recently, Cascione et al determined miRNA expression profiles to stratify TNBCs and identified miRNA signatures that correlated with prognosis and were independent predictors for OS and DFI (36 ). Radojicic et al recently explored the expression profile of miRNAs in TNBC and reported that there was a nonsignificant trend for high expression levels of the miRNAs miR-21, miR-210, miR-221, and miR-222 to be associated with worse patient DFI and OS (37 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Metastasis-Related MicroRNAs in Early Breast Cancer Patients with a Long Follow-up

et al. 2014

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BACKGROUND: Stability of microRNAs (miRNAs) in formalin-fixed paraffin-embedded (FFPE) tissues enables their reliable analysis in archived FFPE tissue samples, which are an invaluable source for the evaluation of novel biomarkers. Especially in breast cancer, for which late relapses occur in many cases, analysis of miRNAs in FFPE tissues holds great potential, because it can lead to the discovery of novel biomarkers suitable for future routine clinical diagnostics for breast cancer. We investigated the prognostic significance of 6 metastasis-related miRNAs that can critically regulate various stages of migration and invasion and play critical roles in the multistep metastatic process.

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“…miRNAs are a highly conserved group of short noncoding RNAs ($22 bp) that play a major role in posttranslational regulation of gene expression and are critical regulators of oncogenic pathways (5). miRNAs have been widely associated with breast cancer tumorigenesis (6), as well as with prognosis and response to treatment in breast cancer (7,8). A recent study by Dvinge and colleagues (9) describes the landscape of miRNA expression in 1,302 primary breast tumors accompanied by matched clinical information and genomic and transcriptomic data (10).…”

Section: Introductionmentioning

confidence: 99%

Tumor Evolution Inferred by Patterns of microRNA Expression through the Course of Disease, Therapy, and Recurrence in Breast Cancer

Dadiani

Ben-Moshe

Paluch‐Shimon

et al. 2016

Clinical Cancer Research

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Purpose: Molecular evolution of tumors during progression, therapy, and metastasis is a major clinical challenge and the main reason for resistance to therapy. We hypothesized that microRNAs (miRNAs) that exhibit similar variation of expression through the course of disease in several patients have a significant function in the tumorigenic process. Experimental design: Exploration of evolving disease by profiling 800 miRNA expression from serial samples of individual breast cancer patients at several time points: pretreatment, posttreatment, lymph nodes, and recurrence sites when available (58 unique samples from 19 patients). Using a dynamic approach for analysis, we identified expression modulation patterns and classified varying miRNAs into one of the eight possible temporal expression patterns. Results: The various patterns were found to be associated with different tumorigenic pathways. The dominant pattern identified an miRNA set that significantly differentiated between disease stages, and its pattern in each patient was also associated with response to therapy. These miRNAs were related to tumor proliferation and to the cell-cycle pathway, and their mRNA targets showed anticorrelated expression. Interestingly, the level of these miRNAs was lowest in matched recurrent samples from distant metastasis, indicating a gradual increase in proliferative potential through the course of disease. Finally, the average expression level of these miRNAs in the pretreatment biopsy was significantly different comparing patients experiencing recurrence to recurrence-free patients. Conclusions: Serial tumor sampling combined with analysis of temporal expression patterns enabled to pinpoint significant signatures characterizing breast cancer progression, associated with response to therapy and with risk of recurrence. Clin Cancer Res; 22(14); 3651–62. ©2016 AACR.

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Integrated MicroRNA and mRNA Signatures Associated with Survival in Triple Negative Breast Cancer

Cited by 166 publications

References 49 publications

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

Prognostic Significance of Metastasis-Related MicroRNAs in Early Breast Cancer Patients with a Long Follow-up

Tumor Evolution Inferred by Patterns of microRNA Expression through the Course of Disease, Therapy, and Recurrence in Breast Cancer

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