Abstract
The hypoxic environment is a crucial component of the cancer stem cell niche and it is capable of eliciting stem cell features in cancer cells. We previously reported that SNAI2 up-regulates the expression of Carbonic Anhydrase iso-enzyme 9 (CA9) in hypoxic MCF7 cells. Here we show that SNAI2 down-regulates miR34a expression in hypoxic MCF7 cell-derived mammospheres. Next, we report on the capability of miR34a to decrease CA9 mRNA stability and CA9 protein expression. We also convey that the over-expression of cloned CA9-mRNA-3'UTR increases the mRNA half-life and protein levels of two miR34a targets JAGGED1 and NOTCH3. The data here reported shows that the SNAI2-dependent down-regulation of miR34a substantially contributes to the post-transcriptional up-regulation of CA9, and that CA9-mRNA-3'UTR acts as an endogenous microRNA sponge. We conclude that CA9/miR34 interplay shares in the hypoxic regulation of mammospheres and therefore, may play a relevant role in the hypoxic breast cancer stem cell niche.
© 2015 Wiley Periodicals, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Neoplasm / biosynthesis*
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Antigens, Neoplasm / genetics
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Breast Neoplasms / genetics*
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Breast Neoplasms / pathology
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Calcium-Binding Proteins / biosynthesis
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Carbonic Anhydrase IX
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Carbonic Anhydrases / biosynthesis*
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Carbonic Anhydrases / genetics
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Cell Hypoxia / genetics*
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Hypoxia / genetics
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Intercellular Signaling Peptides and Proteins / biosynthesis
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Jagged-1 Protein
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MCF-7 Cells
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Membrane Proteins / biosynthesis
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MicroRNAs / biosynthesis
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MicroRNAs / genetics*
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Neoplastic Stem Cells / metabolism
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Neoplastic Stem Cells / pathology
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Receptor, Notch3
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Receptors, Notch / biosynthesis
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Serrate-Jagged Proteins
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Snail Family Transcription Factors
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Transcription Factors / biosynthesis
Substances
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Antigens, Neoplasm
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Calcium-Binding Proteins
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Intercellular Signaling Peptides and Proteins
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JAG1 protein, human
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Jagged-1 Protein
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MIRN34 microRNA, human
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Membrane Proteins
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MicroRNAs
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NOTCH3 protein, human
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Receptor, Notch3
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Receptors, Notch
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SNAI2 protein, human
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Serrate-Jagged Proteins
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Snail Family Transcription Factors
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Transcription Factors
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CA9 protein, human
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Carbonic Anhydrase IX
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Carbonic Anhydrases