Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA263604 | ENA |
REPOSITORIES: ENA
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Project description:MicroRNA profiling of the developing mammary gland identifies miR-184 as a candidate breast tumour suppressor gene (Affymetrix)
| PRJNA263603 | ENA
Project description:The study of mammalian development has offered many insights into the molecular aetiology of cancer. We previously used analysis of mammary morphogenesis to discover a critical role for GATA-3 in mammary developmental and carcinogenesis. In recent years an important role for MicroRNAs (miRNAs) in a myriad of cellular processes in development and in oncogenesis has emerged. In this study, microRNA profiling of stromal and epithelial cellular subsets microdissected from the developing mouse mammary gland revealed many microRNAs with expression restricted to various cellular subsets. MicroRNA-184 (miR-184) was exclusively expressed in epithelial cells and markedly upregulated during differentiation of the proliferative, invasive cells of the pubertal terminal end bud (TEB) into ductal epithelial cells in vivo and in FACS-sorted mammary stem cells (MaSCs) versus luminal epithelial cells. miR-184 expression was silenced in mouse tumour models compared to non-transformed epithelium and in a majority of breast cancer cell line models. Ectopic reactivation of miR-184 inhibited the proliferation and self-renewal of metastatic triple negative breast cancer (TNBC) cell lines in vitro and delayed tumour formation and reduced metastasis in vivo. Gene expression studies uncovered multi-factorial direct regulation of genes in the AKT/mTORC1 pathway by miR-184. In clinical breast cancer tissues, expression of miR-184 is lost in primary TNBCs while the miR-184 promoter is methylated in a subset of lymph node metastases from TNBC patients. These studies elucidated a new layer of regulation in the PI3K/AKT/mTOR pathway with relevance to mammary development and tumour proliferation and metastasis.
2015-10-01 | GSE62259 | GEO
Project description:The study of mammalian development has offered many insights into the molecular aetiology of cancer. We previously used analysis of mammary morphogenesis to discover a critical role for GATA-3 in mammary developmental and carcinogenesis. In recent years an important role for MicroRNAs (miRNAs) in a myriad of cellular processes in development and in oncogenesis has emerged. In this study, microRNA profiling of stromal and epithelial cellular subsets microdissected from the developing mouse mammary gland revealed many microRNAs with expression restricted to various cellular subsets. MicroRNA-184 (miR-184) was exclusively expressed in epithelial cells and markedly upregulated during differentiation of the proliferative, invasive cells of the pubertal terminal end bud (TEB) into ductal epithelial cells in vivo and in FACS-sorted mammary stem cells (MaSCs) versus luminal epithelial cells. miR-184 expression was silenced in mouse tumour models compared to non-transformed epithelium and in a majority of breast cancer cell line models. Ectopic reactivation of miR-184 inhibited the proliferation and self-renewal of metastatic triple negative breast cancer (TNBC) cell lines in vitro and delayed tumour formation and reduced metastasis in vivo. Gene expression studies uncovered multi-factorial direct regulation of genes in the AKT/mTORC1 pathway by miR-184. In clinical breast cancer tissues, expression of miR-184 is lost in primary TNBCs while the miR-184 promoter is methylated in a subset of lymph node metastases from TNBC patients. These studies elucidated a new layer of regulation in the PI3K/AKT/mTOR pathway with relevance to mammary development and tumour proliferation and metastasis.
2015-10-01 | GSE62260 | GEO
Project description:Pancreatic ß-cells adapt to compensate for the increased metabolic demand during insulin resistance. While the microRNA pathway has an essential role in the expansion of ß-cell mass, the extent of its contribution is unclear. Here we show that miR-184 is silenced in the pancreatic islets of several insulin-resistant mouse models and in the islets of type-2 diabetic human subjects. Reduction of miR-184 promotes the expression of its target Argonaute2 (Ago2), a component of the microRNA-induced silencing complex. While over-expression of Ago2 increased ß-cell proliferation, conditional deletion decreased ß-cell number. Moreover, restored expression of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory ß-cell expansion. Loss of Ago2 expression during insulin resistance blocked ß-cell growth and relieved the regulation of miR-375-targeted genes including the growth suppressor Cadm1. This study identifies the regulation of Ago2 by miR-184 as an essential component of the compensatory response to promote proliferation during insulin resistance.
2014-02-06 | GSE46623 | GEO
Project description:Pancreatic M-CM-^_-cells adapt to compensate for the increased metabolic demand during insulin resistance. While the microRNA pathway has an essential role in the expansion of M-CM-^_-cell mass, the extent of its contribution is unclear. Here we show that miR-184 is silenced in the pancreatic islets of several insulin-resistant mouse models and in the islets of type-2 diabetic human subjects. Reduction of miR-184 promotes the expression of its target Argonaute2 (Ago2), a component of the microRNA-induced silencing complex. While over-expression of Ago2 increased M-CM-^_-cell proliferation, conditional deletion decreased M-CM-^_-cell number. Moreover, restored expression of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory M-CM-^_-cell expansion. Loss of Ago2 expression during insulin resistance blocked M-CM-^_-cell growth and relieved the regulation of miR-375-targeted genes including the growth suppressor Cadm1. This study identifies the regulation of Ago2 by miR-184 as an essential component of the compensatory response to promote proliferation during insulin resistance. MIN6 cells were transfected with Doxycyline responsive plasmids including the tetO-184 construct in biological triplicates for every time point. The conditions included untransfected control (CTR, induced), Transfected Control (TC, uninduced) along the time points of miR-184 overexpression in 16, 24, 48, and 72 hours of doxycycline treatment.
2014-02-06 | E-GEOD-46623 | biostudies-arrayexpress
Project description:In this study we identifies miR-21 to by under cytokine control through the transcription factor STAT5 and while miR-21 is differentially expressed during mammary gland development, miR-21 is dispensable for mammary development and lactation.
2013-08-22 | GSE50068 | GEO
Project description:In this study we identifies miR-21 to by under cytokine control through the transcription factor STAT5 and while miR-21 is differentially expressed during mammary gland development, miR-21 is dispensable for mammary development and lactation. We refer to wild-type mice (+/+) as WT and to mice lacking the mir-21 (-/-) as KO mice.
2013-08-22 | E-GEOD-50068 | biostudies-arrayexpress
Project description:Background : In lactating cow, a sunflower oil supplementation modulated the milk composition and the mammary genes expression whose mechanisms of regulations are unclear. Results : This lipid supplementation provoke, in mammary gland, the down regulation of microRNA miR-20a-5p and miR-142-5p, which are predicted to target genes previously determined as differentially expressed including those involved in lipid metabolism. Conclusion : Those two miRNA are good candidates to explain lipogenic genes regulations after sunflower oil supplementation. Significance : The current study clarified the nutriregulation of miRNA in the mammary gland.
2016-07-01 | GSE81616 | GEO
Project description:Mice deficient for miR-212/132 have been reported to show impaired mammary gland development. However, another miR-212/132-deficient line does not demonstrate any obvious defects in mammary gland organogenesis. The transcriptome analysis in the mammary gland of the previously reported miR-212/132-deficient line by deep RNA-seq revealed significantly deregulated expression of genes flanking Mir-212/132 locus, such as HIC1, implying that the mammary gland phenotype might not be only due to loss of miR-212/132
2014-07-29 | GSE37952 | GEO