Triple-negative and luminal A breast tumors: differential expression of miR-18a-5p, miR-17-5p, and miR-20a-5p

Filho, Carlos Marino Cabral Calvano; Calvano-Mendes, Daniele Carvalho; Carvalho, Kátia Cândido; Maciel, Gustavo Arantes Rosa; Ricci, Marcos Desídérío; Torres, Ana Paula Repolês; Filassi, José Roberto; Baracat, Edmund Chada

doi:10.1007/s13277-014-2025-7

Cited by 81 publications

(44 citation statements)

References 42 publications

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“…Li et al . demonstrated that down‐regulation of endogenous miR‐17‐5p suppressed the migration and invasion of MDA‐MB‐231 cells by targeting HBP1 and subsequent activation of Wnt/β‐caten 39, 40. These findings suggest that the differences in the expression of miR‐17‐92 cluster will explain the phenotypic differences between these molecular subtypes of tumours.…”

Section: Resultsmentioning

confidence: 85%

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Analysis of the miRNA–mRNA–lncRNA networks in ER+ and ER− breast cancer cell lines

Guo

Jiang

et al. 2015

J Cellular Molecular Medi

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Recently, rapid advances in bioinformatics analysis have expanded our understanding of the transcriptome to a genome‐wide level. miRNA–mRNA–lncRNA interactions have been shown to play critical regulatory role in cancer biology. In this study, we discussed the use of an integrated systematic approach to explore new facets of the oestrogen receptor (ER)‐regulated transcriptome. The identification of RNAs that are related to the expression status of the ER may be useful in clinical therapy and prognosis. We used a network modelling strategy. First, microarray expression profiling of mRNA, lncRNA and miRNA was performed in MCF‐7 (ER‐positive) and MDA‐MB‐231 cells (ER‐ negative). A co‐expression network was then built using co‐expression relationships of the differentially expressed mRNAs and lncRNAs. Finally, the selected miRNA–mRNA network was added to the network. The key miRNA–mRNA–lncRNA interaction can be inferred from the network. The mRNA and non‐coding RNA expression profiles of the cells with different ER phenotypes were distinct. Among the aberrantly expressed miRNAs, the expression levels of miR‐19a‐3p, miR‐19b‐3p and miR‐130a‐3p were much lower in the MCF‐7 cells, whereas that of miR‐148b‐3p was much higher. In a cluster of miR‐17‐92, the expression levels of six of seven miRNAs were lower in the MCF‐7 cells, in addition to miR‐20b in the miR‐106a‐363 cluster. However, the levels of all the miRNAs in the miR‐106a‐25 cluster were higher in the MCF‐7 cells. In the co‐expression networking, CD74 and FMNL2 gene which is involved in the immune response and metastasis, respectively, had a stronger correlation with ER. Among the aberrantly expressed lncRNAs, lncRNA‐DLEU1 was highly expressed in the MCF‐7 cells. A statistical analysis revealed that there was a co‐expression relationship between ESR1 and lncRNA‐DLEU1. In addition, miR‐19a and lncRNA‐DLEU1 are both located on the human chromosome 13q. We speculate that miR‐19a might be co‐expressed with lncRNA‐DLEU1 to co‐regulate the expression of ESR1, which influences the occurrence and development of breast cancer cells with different levels of ER expression. Our findings reveal that the status of ER is mainly due to the differences in the mRNA and ncRNA profile between the breast cancer cell lines, and highlight the importance of studying the miRNA–mRNA–lncRNA interactions to completely illustrate the intricate transcriptome.

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Section: Resultsmentioning

confidence: 85%

“…Calvano et al . 39 used real‐time RT‐PCR to evaluate the miRNA expression profiles of formalin‐fixed paraffin‐embedded BC tissue. It was found that the expression of miR‐17‐5p, miR‐18a‐5p and miR‐20a‐5 in the triple‐negative tumours (ER−, PR− and HER2−) was higher that of luminal A samples.…”

Section: Resultsmentioning

confidence: 99%

Analysis of the miRNA–mRNA–lncRNA networks in ER+ and ER− breast cancer cell lines

Guo

Jiang

et al. 2015

J Cellular Molecular Medi

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“…Overall these data suggest miR-34a re-introduction in TNBC shuts down oncogenic signaling pathways that affect invasion and proliferation, eventually resulting in cell death by way of cytostasis/senescence. Interestingly, some oncogenic mediators could include non-coding RNAs such as the miR-17/92 cluster, which is known to be elevated in TNBC(28–30) and can be downregulated by miR-34a reintroduction(Fig. S2H).…”

Section: Resultsmentioning

confidence: 99%

miR-34a Silences c-SRC to Attenuate Tumor Growth in Triple-Negative Breast Cancer

et al. 2016

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Triple-negative breast cancer (TNBC) is an aggressive subtype with no clinically proven biologically targeted treatment options. The molecular heterogeneity of TNBC and lack of high frequency driver mutations other than TP53 have hindered the development of new and effective therapies that significantly improve patient outcomes. MicroRNAs (miRNAs), global regulators of survival and proliferation pathways important in tumor development and maintenance, are becoming promising therapeutic agents. We performed miRNA-profiling studies in different TNBC subtypes to identify miRNAs that significantly contribute to disease progression. We found that miR-34a was lost in TNBC, specifically within mesenchymal and mesenchymal-stem cell like subtypes, whereas expression of miR-34a targets were significantly enriched. Furthermore, restoration of miR-34a in cell lines representing these subtypes inhibited proliferation and invasion, activated senescence, and promoted sensitivity to dasatinib by targeting the proto-oncogene c-SRC. Notably, SRC-depletion in TNBC cell lines phenocopied the effects of miR-34a re-introduction, while SRC overexpression rescued the anti-tumorigenic properties mediated by miR-34a. miR-34a levels also increased when cells were treated with c-SRC inhibitors, suggesting a negative-feedback exists between miR-34a and c-SRC. Moreover, miR-34a administration significantly delayed tumor growth of subcutaneously and orthotopically implanted tumors in nude mice, and was accompanied by c-SRC downregulation. Finally, we found that miR-34a and SRC levels were inversely correlated in human tumor specimens. Together, our results demonstrate that miR-34a exerts potent anti-tumorigenic effects in vitro and in vivo, and suggests that miR-34a replacement therapy, which is currently being tested in human clinical trials, represents a promising therapeutic strategy for TNBC.

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“…Hence, we tried to explore the function of miR-20a-5p in colorectal cancer development and we confirmed that miR-20a-5p was upregulated in CRC tissues, especially metastatic tissues than non-metastatic tissues. Not only in CRC, in breast cancers, miR-20a-5p with miR-17–5p and miR-18a-5p, were also increased in triple-negative compared with the luminal A [22]. In nasopharyngeal carcinoma, overexpressed miR-20a-5p combined with miR-24–3p, miR-891a, miR-106a-5p and miR-1908 formed the exosomes to downregulated the MARK1 signaling pathway to alter cell proliferation and differentiation [23].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4

et al. 2016

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BackgroundTumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known.ResultsmiR-20a-5p negatively regulated Smad4 by directly targeting its 3′UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients’ clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients.MethodsFive miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan–Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data.ConclusionsmiR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer.

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Triple-negative and luminal A breast tumors: differential expression of miR-18a-5p, miR-17-5p, and miR-20a-5p

Cited by 81 publications

References 42 publications

Analysis of the miRNA–mRNA–lncRNA networks in ER+ and ER− breast cancer cell lines

Analysis of the miRNA–mRNA–lncRNA networks in ER+ and ER− breast cancer cell lines

miR-34a Silences c-SRC to Attenuate Tumor Growth in Triple-Negative Breast Cancer

MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4

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