Transcription profiling by array of human breast cancer cell lines after treatment with miR-221/222 mimics or inhibitors
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Adai Alex
PROVIDER: S-ECPF-GEOD-10890 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Basal-like breast cancer (BLBC) is an aggressive subtype with a strong tendency to metastasize. Due to the lack of effective chemotherapy, BLBC has a poor prognosis compared with luminal subtype breast cancer. MicroRNA-221 and -222 (miR-221/222) are overexpressed in BLBC and associate with metastasis as well as poor prognosis; however, the mechanisms by which miR-221/222 function as oncomiRs remain unknown. Here, we report that miR-221/222 expression is inversely correlated with Notch3 expression in breast cancer cell lines. Notch3 is known to be overexpressed in luminal breast cancer cells and inhibits epithelial to mesenchymal transition (EMT). We demonstrate that miR-221/222 target Notch3 by binding to its 3' untranslated region and suppressing protein translation. Ectopic expression of miR-221/222 significantly promotes EMT, whereas overexpression of Notch3 intracellular domain attenuates the oncogenic function of miR-221/222, suggesting that miR-221/222 exerts its oncogenic role by negatively regulating Notch3. Taken together, our results elucidated that miR-221/222 promote EMT via targeting Notch3 in breast cancer cell lines suggesting that miR-221/222 can serve as a potential therapeutic target in BLBC.
| S-EPMC6079079 | biostudies-literature
Project description:Analysis of gene expression of MCF10A to identify the targets of miR-221 and miR-222 Keywords: MCF10, miR-221, miR-222 RNA profiles of human MCF10A cell line
| S-ECPF-GEOD-29327 | biostudies-other
Project description:BackgroundMiR-221/-222 are frequently overexpressed in breast cancer and are associated with increased malignancy. The specific modification of microRNAs (miRNAs) expression could be a promising strategy in breast cancer therapy, leading to the suppression of tumourigenic processes in tumour cells.MethodsMiR-221/-222 expressions were analysed in 86 breast cancer tissues by quantitative RT-PCR and tested for correlation with immunohistochemistry data and clinical follow-up. In vitro assays were conducted using human breast cancer cell lines with lentiviral overexpression of miR-221/-222.ResultsIn tumour tissues, miR-221/-222 were associated with the occurrence of distant metastases. In particular, high levels of miR-221 were revealed to have a high prognostic impact for the identification of significantly different groups with advanced tumours. MiR-221/-222 overexpression strongly increased cell proliferation and invasion in vitro. Following miR-221/-222 overexpression an increased uPAR expression and cell invasion were observed.ConclusionThis study demonstrates a significant role for highly expressed miR-221/-222 in advanced breast cancers allowing for the identification of significantly different prognostic groups, particularly for HER2-positive and lymph-node-positive breast cancers. Considering that miR-221/-222 are strongly involved in cell invasion, these miRNAs may be promising markers for breast cancer prognosis and therapy.
| S-EPMC3833215 | biostudies-literature
Project description:Primary outcome(s): Presence of colorectal adenoma or gastrointestinal cancers
| 2630284 | ecrin-mdr-crc
Project description:Breast malignancy remains one of the most common causes of cancer-associated mortalities among women. MicroRNA (miR)-221 and miR-222 are homologous miRs and have a substantial impact on cancer progression. In the present study, the regulatory mechanisms of miR-221/222 and its target annexin A3 (ANXA3) in breast cancer cells were investigated. Breast tissue samples were collected to evaluate the expression patterns of miR-221/222 levels in breast cancer cell lines and cancer tissues according to clinical characteristics. The levels of miR-221/222 were increased or decreased in cancer cell lines compared with normal breast cell lines according to cell line subtype. Subsequently, the changes in the progression and invasion of breast cancer cells were investigated using cell proliferation, invasion assay, gap closure and colony formation assays. Western blotting of cell cycle proteins and flow cytometry were performed to evaluate the possible pathway of miR-221/222 and ANXA3 axis. Chemosensitivity tests were performed to explore the suitability of the miR-221/222 and ANXA3 axis as a therapeutic target in breast cancer. The expression levels of miR-221/222 were associated with aggressive characteristics of breast cancer subtypes. Cell transfection assay demonstrated the regulation of breast cancer proliferation and invasiveness by miR-221/222. MiR-221/222 directly targeted the 3'-untranslated region of ANXA3 and suppressed the expression of ANXA3 at the mRNA and protein levels. In addition, miR-221/222 negatively regulated cell proliferation and the cell cycle pathway in breast cancer cells by targeting ANXA3. In combination with adriamycin, downregulation of ANXA3 may sensitize adriamycin-induced cell death to induction of persistent G2/M and G0/G1 arrest. Decreased expression of ANXA3 through increased expression of miR-221/222 reduced breast cancer progression and increased the effectiveness of the chemotherapy drug. The present results indicated the miR-221/222 and ANXA3 axis to be a possible novel therapeutic target for the treatment of breast cancer.
| S-EPMC9947582 | biostudies-literature
Project description:PurposeMicroRNAs (miRNAs) regulate various cellular functions, including development, cell proliferation, apoptosis, and tumorigenesis. Different signatures associated with various tissue types, diagnosis, progression, prognosis, staging, and treatment response have been identified by miRNA expression profiling of human tumors. miRNAs function as oncogenes or as tumor suppressors. The relationship between gastric cancer and miRNA garnered attention due to the high incidence of gastric cancer in Asian countries. miR-222/221 expression increases in gastric tumor tissues. The oncogenic effect of miR-222/221 was previously determined in functional studies and xenograft models. In this study, transgenic mice over-expressing miR-222/221 were generated to confirm the effect of miR-222/221 on gastric carcinogenesis.Materials and methodsAt 6 weeks of age, 65 transgenic mice and 53 wild-type mice were given drinking water containing N-nitroso-N-methylurea (MNU) for 5 alternating weeks to induce gastric cancer. The mice were euthanized at 36 weeks of age and histologic analysis was performed.ResultsHyperplasia was observed in 3.77% of the wild-type mice and in 18.46% of the transgenic mice (p=0.020). Adenoma was observed in 20.75% of the wild-type mice and 26.15% of the transgenic mice (p=0.522). Carcinoma was observed in 32.08% of the wild-type mice and 41.54% of the transgenic mice (p=0.341). The frequency of hyperplasia, adenoma, and carcinoma was higher in transgenic mice, but the difference was statistically significant only in hyperplasia.ConclusionThese results suggest that hyperplasia, a gastric pre-cancerous lesion, is associated with miR-222/221 expression but miR-222/221 expression does not affect tumorigenesis itself.
| S-EPMC5266385 | biostudies-literature
Project description:Analysis of gene expression of MCF10A to identify the targets of miR-221 and miR-222 Keywords: MCF10, miR-221, miR-222
2011-06-14 | GSE29327 | GEO
Project description:Glioblastoma multiforme (GBM) is one of the most deadly types of cancer. To date, the best clinical approach for treatment is based on administration of temozolomide (TMZ) in combination with radiotherapy. Much evidence suggests that the intracellular level of the alkylating enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) impacts response to TMZ in GBM patients. MGMT expression is regulated by the methylation of its promoter. However, evidence indicates that this is not the only regulatory mechanism present. Here, we describe a hitherto unknown microRNA-mediated mechanism of MGMT expression regulation. We show that miR-221 and miR-222 are upregulated in GMB patients and that these paralogues target MGMT mRNA, inducing greater TMZ-mediated cell death. However, miR-221/miR-222 also increase DNA damage and, thus, chromosomal rearrangements. Indeed, miR-221 overexpression in glioma cells led to an increase in markers of DNA damage, an effect rescued by re-expression of MGMT. Thus, chronic miR-221/222-mediated MGMT downregulation may render cells unable to repair genetic damage. This, associated also to miR-221/222 oncogenic potential, may poor GBM prognosis.
| S-EPMC3798259 | biostudies-literature
Project description:BackgroundCardiovascular disease is the leading cause of death worldwide. Cardiac electrical remodeling including altered ion channel expression and imbalance of calcium homeostasis can have detrimental effects on cardiac function. While it has been extensively reported that miR-221/222 are involved in structural remodeling, their role in electrical remodeling still has to be evaluated. We previously reported that subunits of the L-type Ca2+ channel (LTCC) are direct targets of miR-221/222. Furthermore, HL-1 cells transfected with miR-221 or -222 mimics showed a reduction in LTCC current density while the voltage-dependence of activation was not altered. The aim of the present study was to determine the influence of miR-221/222 on cardiomyocyte calcium handling and function.ResultsTransient transfection of HL-1 cells with miR-221/222 mimics led to slower depolarization-dependent Ca2+ entry and increased proportion of non-responding cells. Angiotensin II-induced Ca2+ release from the SR was not affected by miR-221/222. In miR-222-transfected neonatal cardiomyocytes the isoprenaline-induced positive inotropic effect on the intracellular Ca2+ transient was lost and the positive chronotropic effect on spontaneous beating activity was strongly reduced. This could have severe consequences for cardiomyocytes and could lead to a reduced contractility and systolic dysfunction of the whole heart.ConclusionsThis study adds a new role of miR-221/222 in cardiomyocytes by showing the impact on β-adrenergic regulation of LTCC function, calcium handling and beating frequency. Together with the previous report that miR-221/222 reduce GIRK1/4 function and LTCC current density, it expands our knowledge about the role of these miRs on cardiac ion channel regulation.
| S-EPMC8369661 | biostudies-literature
Project description:The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT) and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a much higher expression of miR-221/222 in highly invasive basal-like breast cancer (BLBC) cells than that in non-invasive luminal cells. A microRNA dataset from breast cancer patients indicated an elevated expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was associated with the induction of miR-221/222 expression. miRNA inhibitors specially targeting miR-221 or miR-222 both significantly suppressed cellular migration, invasion and G1/S transition of the cell cycle in BLBC cell types. Proteomic analysis demonstrated the down-regulation of two tumor suppressor genes, suppressor of cytokine signaling 1 (SOCS1) and cyclin-dependent kinase inhibit 1B (CDKN1B), by miR-221/222. This is the first report to reveal miR-221/222 regulation of G1/S transition of the cell cycle. These findings demonstrate that miR-221/222 contribute to the aggressiveness in control of BLBC.
| S-EPMC6271560 | biostudies-literature