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Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration

ABSTRACT: The progression of cancer to metastatic disease is a major cause of death. We identified miR-708 being transcriptionally repressed by polycomb repressor complex (PRC2)-induced H3-K27 trimethylation in metastatic breast cancer. miR-708 targets the endoplasmic reticulum protein neuronatin (Nnat) to decrease intracellular calcium (Ca2+) level, resulting in reduction of activation of ERK and FAK, decreased cell migration, and impaired metastases. Functional complementation experiments with Nnat-3’UTR mutant, which is refractory to suppression by miR-708, rescued cell migration and metastasis defects. In breast cancer patients, miR-708 expression was decreased in lymph node and distal metastases, suggesting a metastasis-suppressive role. Our findings uncover a mechanistic role for miR-708 in metastasis and provide a rationale for developing miR-708 as a therapeutic agent against metastatic breast cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE42313 | GEO | 2013/11/15

SECONDARY ACCESSION(S): PRJNA181009

REPOSITORIES: GEO

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Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration

Project description:The progression of cancer to metastatic disease is a major cause of death. We identified miR-708 being transcriptionally repressed by polycomb repressor complex (PRC2)-induced H3-K27 trimethylation in metastatic breast cancer. miR-708 targets the endoplasmic reticulum protein neuronatin (Nnat) to decrease intracellular calcium (Ca2+) level, resulting in reduction of activation of ERK and FAK, decreased cell migration, and impaired metastases. Functional complementation experiments with Nnat-3’UTR mutant, which is refractory to suppression by miR-708, rescued cell migration and metastasis defects. In breast cancer patients, miR-708 expression was decreased in lymph node and distal metastases, suggesting a metastasis-suppressive role. Our findings uncover a mechanistic role for miR-708 in metastasis and provide a rationale for developing miR-708 as a therapeutic agent against metastatic breast cancer. Sequencing miRNAs from Human breast cancer cells: MCF10A, MCF7, MDA-MB-231, MDA-MB-LM2

2013-11-15 | E-GEOD-42313 | biostudies-arrayexpress

Increased miR-708 expression in NSCLC and its association with poor survival in lung adenocarcinoma from Never Smokers

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Increased miR-708 expression in NSCLC and its association with poor survival in lung adenocarcinoma from Never Smokers

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Stress-regulated miR-708-5p affects recognition memory and manic-like behavior through Neuronatin downregulation.

Project description:microRNAs are posttranscriptional regulators that bind to target mRNAs. We tested the regulatory effect of miR-708-5p, a miRNA associated with Bipolar Disorder, in the mouse hippocampus. To unveil molecular mechanisms downstream of miR-708-5p, we stereotactically injected a virus overexpressing miR-708-5p for target discovery.

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Transcriptomic analysis of the hypothalamic paraventricular and the arcuate nucleus of NNAT null mice

Project description:Neuronatin (Nnat) has previously been reported to be part of a network of imprinted genes. Disruption of neuronatin results in an unusual phenotype of a bimodal body weight.In order to understand at the molecular level how the Nnat deficiency could contribute to the hypervariable phenotypes seen, we performed RNA sequencing from laser-capture micro dissected paraventricular nucleus (PVN) and arcuate nucleus (ARC) and compared the transcriptome between Nnat+/-p mice and their Nnat+/+ littermates in different feeding conditions. We performed an analysis of three subgroups: Nnat+/+ (all non-obese), Nnat+/-p non-obese, and Nnat+/-p obese mice and combined two approaches to identify differences in hypothalamic gene expression between subgroups

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ABCC5 supports osteoclast formation and promotes breast cancer metastasis to bone

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2021-09-08 | PXD012286 | Pride

ABCC5 supports osteoclast formation and promotes breast cancer metastasis to bone

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Stress-regulated miR-708-5p affects recognition memory and manic-like behavior through Neuronatin downregulation.

Project description:Stress-regulated miR-708-5p affects recognition memory and manic-like behavior through Neuronatin downregulation.

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