Gene/Protein
Disease
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Drug
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Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
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Query: UMLS:C1384489 (
Scratch
)
395
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Bone morphogenetic protein 4
(
BMP4
) is a remarkably powerful inhibitor of breast cancer cell proliferation, but it is also able to induce breast cancer cell migration in certain cellular contexts. Previous data demonstrate that
BMP4
controls the transcription of a variety of protein-coding genes, but not much is known about microRNAs (miRNA) regulated by
BMP4
. To address this question, miRNA expression profiles following
BMP4
treatment were determined in one mammary epithelial and seven breast cancer cell lines using microarrays. While the analysis revealed an extensive variation in differentially expressed miRNA across cell lines, four miRNAs (miR-16-5p, miR-106b-5p, miR-23a-3p, and miR-23b-3p) were commonly induced in a subset of breast cancer cells upon
BMP4
treatment. Inhibition of their expression demonstrated an increase in BT-474 cell number, indicating that they possess tumor suppressive properties. However, with the exception of miR-106b-5p, these effects were independent of
BMP4
treatment.
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assay with miR-16-5p and miR-106b-5p inhibitors on
BMP4
-treated MDA-MB-231 cells resulted in enhanced cell migration, suggesting that these miRNAs are engaged in
BMP4
-induced motility. Taken together, we have for the first time characterized the
BMP4
-induced miRNA expression profiles in breast cancer cell lines, showing that induced miRNAs contribute to the fine-tuning of proliferation and migration phenotypes.
...
PMID:Bone morphogenetic protein 4 regulates microRNA expression in breast cancer cell lines in diverse fashion. 2668 38
Glioblastoma multiforme (GBM) is a brain tumor that deeply infiltrates adjacent tissues and causes significant mortality. Thus, understanding the mechanisms that derive the invasion of brain tissue by GBM might help the treatment of this cancer. To this end, we examined the impact of
BMP4
on invasion of GBM. In this study, Human GBM samples, GBM cells and human orthotopic GBM-xenografted animal model, quantitative PCR, immunostaining, immunoblotting,
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wound and transwell assays were used to detect the effect and the mechanism of
BMP4
in GBM cells.
BMP4
expression was found to positively correlate with E-cadherin and claudin expression in human GBM samples. Elevation or suppression of
BMP4
expression resulted in a respective increase or decrease in E-cadherin and claudin levels, both
in vitro
and
in vivo
. Suppression of
BMP4
expression was associated with enhanced GBM cell migration and invasion, while
BMP4
overexpression inhibited these processes. Smad1/5/8 protein phosphorylation positively correlated with
BMP4
expression. Pharmacological blockade of Smad1/5/8 phosphorylation impaired
BMP4
-dependent inhibition of cell migration and invasion. Together, these findings suggest that
BMP4
increases E-cadherin and claudin expression in GBM through activation of SMAD signaling, thereby suppressing tumor cell invasion.
...
PMID:BMP4 inhibits glioblastoma invasion by promoting E-cadherin and claudin expression. 3084 30