MicroRNA expression signature in estrogen receptor-positive and -negative breast cancers
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE121172 | GEO | 2018/10/13
REPOSITORIES: GEO
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Project description:Breast cancer is a heterogeneous disease encompassing a number of phenotypically diverse tumours. Expression levels of the estrogen, progesterone and HER2/neu receptors which characterise clinically distinct breast tumors have been shown to change during disease progression and in response to systemic therapies. Mi(cro)RNAs play critical roles in diverse biological processes and are aberrantly expressed in several human neoplasms including breast cancer, where they function as regulators of tumour behaviour and progression. The aims of this study were to identify miRNA signatures that accurately predict the oestrogen receptor (ER), progesterone receptor (PR) and HER2/neu receptor status of breast cancer patients to provide insight into the regulation of breast cancer phenotypes and progression. Expression profiling of 353 microRNAs was performed in 29 early stage breast cancer specimens. MiRNA signatures associated with ER, PR and HER2/neu status were generated using artificial neural networks (ANN) and expression of specific microRNAs was validated using RQ-PCR. Results: Stepwise artificial neural network (ANN) analysis identified predictive miRNA signatures corresponding with estrogen (miR-342, miR-299, miR-217, miR -190, miR-135b, miR-218), progesterone (miR-520g, miR-377, miR-527-518a, miR-520f-520c) and HER2/neu (miR-520d, miR-181c, miR-302c, miR-376b, miR-30e) receptor status. MiR-342 and miR-520g expression was further analysed in 95 breast tumours. MiR-342 expression was highest in ER and HER2/neu positive luminal B tumours and lowest in triple-negative tumours. MiR-520g expression was elevated in ER and PR negative tumours.
2010-05-18 | E-GEOD-15885 | biostudies-arrayexpress
Project description:High levels of factor XI (FXI) increase the risk of thromboembolic disease. However, the genetic and environmental factors regulating FXI expression are still largely unknown. The aim of our study was to evaluate the regulation of FXI by microRNAs (miRNAs) in the human liver. In silico prediction yielded four miRNA candidates that might regulate FXI expression. HepG2 cells were transfected with miR-181a-5p, miR- 23a-3p, miR-16-5p and miR-195-5p. We used mir-494, which was not predicted to bind to F11, as a negative control. Only miR-181a-5p caused a significant decrease both in FXI protein and F11 mRNA levels. In addition, transfection with a miR-181a-5p inhibitor in PLC/PRF/5 hepatic cells increased both the levels of F11 mRNA and extracellular FXI. Luciferase assays in human colon cancer cells deficient for Dicer (HCT-DK) demonstrated a direct interaction between miR-181a-5p and 3'untranslated region of F11. Additionally, F11 mRNA levels were inversely and significantly correlated with miR-181a-5p levels in 114 healthy livers, but not with miR-494. This study demonstrates that FXI expression is directly regulated by a specific miRNA, miR-181a-5p, in the human liver. Future studies are necessary to further investigate the potential consequences of miRNA dysregulation in pathologies involving FXI.
2014-10-01 | GSE61219 | GEO
Project description:We used a genome-wide approach (High-throughput sequencing of RNA isolated by crosslinking immunoprecipitation, or HITS-CLIP) to define direct miRNA-mRNA interactions in three breast cancer subtypes (estrogen receptor positive, Her2 amplified and triple negative). Focusing on steroid receptor signaling, we identified two novel regulators of the ER pathway (miR-9-5p and miR-193a/b-3p), which together target multiple genes involved in ER signaling. Moreover, this approach enabled the definition of miR-9-5p as a global regulator of steroid receptor signaling in breast cancer. Finally, we show that miRNA targets and networks defined by our analysis are predictive of patient outcomes and provide global insight into miRNA regulation in breast cancer. Argonaute HITS-CLIP on three representative breast cancer cell lines (each in triplicate).
2014-08-04 | E-GEOD-57855 | biostudies-arrayexpress
Project description:We used a genome-wide approach (High-throughput sequencing of RNA isolated by crosslinking immunoprecipitation, or HITS-CLIP) to define direct miRNA-mRNA interactions in three breast cancer subtypes (estrogen receptor positive, Her2 amplified and triple negative). Focusing on steroid receptor signaling, we identified two novel regulators of the ER pathway (miR-9-5p and miR-193a/b-3p), which together target multiple genes involved in ER signaling. Moreover, this approach enabled the definition of miR-9-5p as a global regulator of steroid receptor signaling in breast cancer. Finally, we show that miRNA targets and networks defined by our analysis are predictive of patient outcomes and provide global insight into miRNA regulation in breast cancer.
2014-08-04 | GSE57855 | GEO
Project description:Dysregulation of microRNA (miRNA) expression contributes to the pathogenesis of several clinical conditions. The aim of this study is to evaluate the associations between miRNAs and childhood acute lymphoblastic leukemia (ALL) to discover their clinical and therapeutic implications. Forty-three children with ALL and 14 age-matched healthy controls were included in the study. MicroRNA microarray expression profiling was used for peripheral blood and bone marrow samples. Aberrant miRNA expressions associated with the diagnosis and outcome were prospectively evaluated. Confirmation analysis was performed by real time RT-PCR. miR-128, miR-146a, miR-155, miR-181a, miR-195 were significantly dysregulated in ALL patients at day 0. Following a six-month treatment period, the change in miRNA levels was determined by real time RT-PCR and expression of miR-146a, miR-155, miR-181a, miR-195 significantly decreased.
2014-04-05 | GSE56489 | GEO
Project description:Dysregulation of microRNA (miRNA) expression contributes to the pathogenesis of several clinical conditions. The aim of this study is to evaluate the associations between miRNAs and childhood acute lymphoblastic leukemia (ALL) to discover their clinical and therapeutic implications. Forty-three children with ALL and 14 age-matched healthy controls were included in the study. MicroRNA microarray expression profiling was used for peripheral blood and bone marrow samples. Aberrant miRNA expressions associated with the diagnosis and outcome were prospectively evaluated. Confirmation analysis was performed by real time RT-PCR. miR-128, miR-146a, miR-155, miR-181a, miR-195 were significantly dysregulated in ALL patients at day 0. Following a six-month treatment period, the change in miRNA levels was determined by real time RT-PCR and expression of miR-146a, miR-155, miR-181a, miR-195 significantly decreased. Forty-three children with ALL and 14 age-matched healthy controls were included in the study.
2014-04-05 | E-GEOD-56489 | biostudies-arrayexpress
Project description:Comparison af adherent growing breast cancer cell lines versus mammospheres under serum-free conditions Background: In patients with breast cancer, subsets of long-lived cells tolerate chemotherapies. These chemoresistant cells can remain dormant at secondary sites, such as bone and lung, for years and decades. Cancer cells endowed with drug resistance are maintained in vivo in a quiescent slow-growing state that preserves them from anti-proliferative cancer drugs. The mechanism of conversion from dormancy to growth remains poorly understood. We aimed to identify microRNAs (miRNAs) as master regulators of cancer stem cells (CSCs) maintainance, because one of the characteristics of CSCs is their slow proliferation or dormancy. MiRNA targeting CSCs may be an effective therapy to improve the prognosis of breast cancer patients. Methods: We performed miRNA array analysis to identify differences miRNA expression profiles between adherent cells and mammospheres that contain higher number of breast cancer stem cells (BCSCs). In this approach, we focused on expression of hsa-miR-27a. Further, roles of hsa-miR-27a target genes in maintaining BCSC properties were analysed . Results: Here, we showed that hsa-miR-27a was downregulated in mammosphere cells. The formation of BCSCs was attenuated by transfection of hsa-miR-27a. We found that hsa-miR-27a targets F-box and WD-40 domain protein 7 (FBW7), a tumor suppressor gene, thereby inducing tumor dormancy. Additionally, we found that hsa-miR-27a targets genes involved in GSH synthesis, including xCT (encoded by SLC7A11), a heterodimeric protein of a transporter subunit of the xC(-) system, cystathionine gamma-lyase (CTH/CSE), and nuclear factor-erythroid 2-related factor 2 (Nrf2/NFE2L2), thereby increasing intracellular reactive oxygen species (ROS) levels. Upregulation of these genes by antisense (as)-miR-27a induced autophagy. Conclusions: Previous studies showed that expression of hsa-miR-27a is elevated in breast cancer. Here, we showed that expression of hsa-miR-27a was reduced in BCSC. CSCs in the dormant state are resistant to chemotherapy due to inhibition of ROS accumulation in these cells. These results demonstrate that hsa-miR-27a plays an essential role in maintaining the BCSCs phenotype via regulation of FBW7, ROS related genes and the Nrf2 pathway, as well as in the dormant-to-proliferative switch of breast cancer cells. Thus, hsa-miR-27a represents a novel strategy for various type of breast cancer.
2019-03-06 | GSE127849 | GEO
Project description:To identify microRNAs impacting estrogen receptor ERα expression in breast cancer, we have screened ER-positive breast cancer cells with a library of pre-miRs, and systematically monitored the ERα expression by protein lysate microarrays. There was a significant enrichment of the in silico predicted ERα targeting microRNAs among the hits. The most potent pre-miRs miR-18a/b, miR-193b, miR-206, and miR-302c, were confirmed to directly target ERα and to repress estrogen-responsive genes. The effect of miRNA overexpression on gene expression profile of MCF-7 cells was studied. Furthermore, miR-18a and miR-18b showed increased expression in ERα-negative as compared to ERα-positive clinical tumors. In summary, we present systematic and direct functional and correlative clinical evidence on microRNAs inhibiting ERα signaling in breast cancer. MCF-7 cells (300 000 per well on 6-well plates) were transfected with an siRNA for ERα or with Ambion pre-miR� constructs for miR-18a, miR-193b, miR-206, miR-302c, or pre-miR negative control #1 (scrambled pre-miR) at 20 nM, and incubated for 24h.
2010-04-09 | E-GEOD-14847 | biostudies-arrayexpress
Project description:To identify microRNAs impacting estrogen receptor ERα expression in breast cancer, we have screened ER-positive breast cancer cells with a library of pre-miRs, and systematically monitored the ERα expression by protein lysate microarrays. There was a significant enrichment of the in silico predicted ERα targeting microRNAs among the hits. The most potent pre-miRs miR-18a/b, miR-193b, miR-206, and miR-302c, were confirmed to directly target ERα and to repress estrogen-responsive genes. The effect of miRNA overexpression on gene expression profile of MCF-7 cells was studied. Furthermore, miR-18a and miR-18b showed increased expression in ERα-negative as compared to ERα-positive clinical tumors. In summary, we present systematic and direct functional and correlative clinical evidence on microRNAs inhibiting ERα signaling in breast cancer.
2009-08-18 | GSE14847 | GEO