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Effects of YB-1 protein reduction on microRNA abundance in breast cancer cell-lines

ABSTRACT: To assess the association of the nucleic acid binding protein yb-1 with mature microRNAs levels in breast cancer. To do this we performed YB-1 siRNA treatement in triplicates alongside an siRNA control Two breast cancer cell-lines, representative of Luminal A and Basal molecular subtypes were used, MCF7 and MDA-MB-435S.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE50087 | GEO | 2014/01/23

SECONDARY ACCESSION(S): PRJNA216148

REPOSITORIES: GEO

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Effects of YB-1 protein reduction on microRNA abundance in breast cancer cell-lines

Project description:To assess the association of the nucleic acid binding protein yb-1 with mature microRNAs levels in breast cancer. To do this we performed YB-1 siRNA treatement in triplicates alongside an siRNA control Two breast cancer cell-lines, representative of Luminal A and Basal molecular subtypes were used, MCF7 and MDA-MB-435S. Two cell-lines, treated with either siYB-1 or si-Ctrl in triplicate samples.

2014-01-23 | E-GEOD-50087 | biostudies-arrayexpress

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Mechanism and transcriptional program of YB-1 in breast cancer cell lines.

Project description:YB-1 controls epithelial-mesenchymal transitions by restricting translation of growth-related mRNAs and enabling expression of EMT-inducing transcription factors. We used microarrays to characterize the direct transcriptional and indirect translational regulation of mRNAs by exogenous YB-1 in breast cancer cell lines. Keywords: gene expression profiling To evaluate this in a genome-wide manner we compared microarray expression profiles of total mRNA and mRNAs isolated from Ps (translationally active) or post-Ps (translationally inactive) fractions of MCF10AT-MSCV vs. MCF10AT-YB-1 cells

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Project description:For patients with triple negative breast tumours (TNBCs), lacking receptors for oestrogen, progesterone or HER2 on their cell surface, chemotherapy is the main treatment. The taxanes, paclitaxel (PTX) and docetaxel, have become the most commonly-used chemotherapies for these kinds of breast cancer. Although several targeted therapies are currently undergoing clinical trials for TNBC, because of the heterogeneous nature of TNBCs, it is predicted that these may often be used in combination with chemotherapy. Therefore an understanding of the mechanisms of chemotherapy resistance will continue to be important for the treatment of these patients. Given the pleiotropic nature of YB-1, the aim of this study was to understand whether there were mechanisms in addition to those discussed above, by which YB-1 controls response to PTX in TNBCs. We initially followed up two previously studied mechanisms, mediated by ABCB1/MDR1 and DUSP4. We then proceeded to use genomics to identify novel mechanisms by which YB-1 regulates the response of TNBCs to PTX. This analysis identified and experimentally validated EGR1, encoding the early growth response protein 1 (EGR1) as a previously undiscovered mechanism of YB-1-driven PTX resistance.

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Project description:Female sterile (1) Yb (Yb) is a primary component of Yb bodies, perinuclear foci known as the site of PIWI-interacting RNA (piRNA) biogenesis in Drosophila ovarian somatic cells. Yb consists of Helicase C-terminal (Hel-C), RNA helicase and extended Tudor (eTud) domains. We previously showed that the RNA helicase domain is necessary for Yb−RNA interaction, Yb body formation and piRNA biogenesis. Here, we investigated the functions of the two other domains and found that Hel-C and eTud are necessary for Yb to self-associate and to interact with RNAs and other Yb body components, respectively. Both domains were essential for Yb body formation and transposon silencing. Without eTud, piRNA production was completely impaired. Loss of Hel-C severely reduced the levels of transposon-targeting piRNAs, although genic piRNAs unrelated to transposon silencing were still produced. Similar phenotypes were observed when mutations in flamenco, the primary source of transposon-targeting piRNAs, led to the expression of attenuated RNAs. Yb bodies are liquid-like multivalent condensates whose assembly depends on Yb self-association and widespread Yb−flamenco RNA binding.

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