Dataset Information

The novel microRNAs hsa-miR-nov7 and hsa-miR-nov3 are over-expressed in locally advanced breast cancer

ABSTRACT: We analyzed small RNA massive parallel sequencing data from 50 locally advanced breast cancers aiming to identify novel breast cancer related microRNAs. We successfully predicted 10 novel miRNAs, out of which 2 (hsa-miR-nov3 and hsa-miR-nov7) were recurrent. Applying high sensitivity qPCR, we detected these two microRNAs in 206 and 214 out of 223 patients in the study from which the initial cohort of 50 samples were drawn. We found hsa-miR-nov3 and hsa-miR-nov7 both to be overexpressed in tumor versus normal breast tissue in a separate set of 13 patients from whom both tumor tissue and normal tissue were available. We observed hsa-miR-nov3 to be expressed at higher levels in ER-positive compared to ER-negative tumors. Further stratifications revealed particularly low levels in the her2-like and basal-like cancers compared to other subtypes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE145151 | GEO | 2020/03/19

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Specificity of interaction between a microRNA (miRNA) and its targets crucially depends on the seed region located in its 5’-end. It is often implicitly considered that two miRNAs sharing the same biological activity should display similarity beyond the strict six nucleotide region that forms the seed, in order to form specific complexes with the same mRNA targets. We have found that expression of hsa-miR-147b and hsa-miR-210, though triggered by different stimuli (i.e. lipopolysaccharides and hypoxia, respectively), induce very similar cellular effects in term of proliferation, migration and apoptosis. Hsa-miR-147b only shares a “minimal” 6-nucleotides seed sequence with hsa-miR-210, but is identical with hsa-miR-147a over 20 nucleotides, except for one base located in the seed region. Phenotypic changes induced after heterologous expression of miR-147a strikingly differ from those induced by miR-147b or miR-210. In particular, miR-147a behaves as a potent inhibitor of cell proliferation and migration. These data fit well with the gene expression profiles observed for miR-147b and miR-210, which are very similar, and the gene expression profile of miR-147a, which is distinct from the two others. Bioinformatics analysis of all human miRNA sequences indicates multiple cases of miRNAs from distinct families exhibiting the same kind of similarity that would need to be further characterized in terms of putative functional redundancy. Besides, it implies that functional impact of some miRNAs can be masked by robust expression of miRNAs belonging to distinct families. To compare the set of transcripts targeted by hsa-miR-147a, hsa-miR-147b and hsa-miR-210, we overexpressed these miRNAs in human lung adenocarcinoma A549 cells by transfecting them with synthetic pre-miRNAs or a synthetic “negative” pre-miRNA as a control (miR-Neg). RNA samples were harvested at 48 hours post-transfection and 3 independent experiments were carried out. 48 hours post-transfection, 3 independent experiments were performed in dye-swap: hsa-miR-147a versus miR-Neg; hsa-miR-147b versus miR-Neg; hsa-miR-210 versus miR-Neg.

Project description:Hemopoiesis entails a series of hierarchically organized events that proceed throughout cell specification and terminates with cell differentiation. Commitment needs the transcription factors effort that, in concert with microRNAs, drives cell fate specification, answering to promiscuous patterns of gene expression by turning on lineage-specific genes and repressing alternate lineage transcripts. Therefore microRNAs and mRNAs cooperate to direct cell fate decisions. We obtained microRNAs profiles from human CD34+ hemopoietic progenitor cells and in-vitro differentiated erythroblasts, megakaryoblasts, monoblasts and myeloblasts precursors and we analyzed them together with the gene expression profiles of the same populations. We found that for most part of microRNAs specifically up-regulated in one single cell progeny an inverse correlation between microRNAs and down-regulated putative targets expression levels occurs. We chose hsa-mir-299-5p as a model to get further insights into the possible biological relevance of this microRNAs-mRNAs expression integrated analytical approach and we asked if the forced expression of a single lineage-specific microRNA is able to control the cell fate of CD34+ progenitors grown in multilineage culture conditions. Gain and loss of-function experiments established that mir-299-5p regulates hemopoietic progenitors fate modulating reciprocally megakaryocytic-granulocytic versus erythroid-monocytic differentiation and has at least two genuine targets, the transcription factors CTCF and SOX4. CD34+ hematopoietic progenitor cells were transfected with the Amaxa Nucleofector Device, using the Human CD34 Cell Nucleofection Kit, accordingly to the manufacturer’s instructions (Amaxa Biosystem, Cologne, Germany), and 5µg of either the Pre-miR miRNA Precursor Molecule—Negative Control # 1 (NC1) or the hsa-mir-299-5p Pre-miR miRNA Precursor Molecule (299-5p) (Ambion, Austin, TX, USA) and pulsed with the program U-008. The dataset is composed of three independent paired experiment of 299-5p gain of-function (three hsa-299-5p Pre-miR miRNA Precursor Molecule nucleoporated samples and three paired Pre-miR miRNA Precursor Molecule—Negative Control # 1 transfected ones).

Dataset Information

The novel microRNAs hsa-miR-nov7 and hsa-miR-nov3 are over-expressed in locally advanced breast cancer

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure