title: Carbonic Anhydrase 9 mRNA/microRNA34a Interplay in Hypoxic Human Mammospheres.
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.
authors.affiliation: Center for Applied Biomedical Research (CRBA), St. Orsola-Malpighi University Hospital, Bologna, Italy.|Department of Experimental, Diagnostic, Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: De Carolis
authors.affiliation: Center for Applied Biomedical Research (CRBA), St. Orsola-Malpighi University Hospital, Bologna, Italy.|Department of Experimental, Diagnostic, Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Bertoni
authors.affiliation: Center for Applied Biomedical Research (CRBA), St. Orsola-Malpighi University Hospital, Bologna, Italy.|Department of Experimental, Diagnostic, Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Nati
authors.affiliation: Center for Applied Biomedical Research (CRBA), St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: D'Anello
authors.affiliation: Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Papi
authors.affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Biosciences Laboratory, Meldola, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Tesei
authors.affiliation: Department of Experimental, Diagnostic, Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Cricca
authors.affiliation: Center for Applied Biomedical Research (CRBA), St. Orsola-Malpighi University Hospital, Bologna, Italy.|Department of Experimental, Diagnostic, Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Bonafé
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis* / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D000072100:Jagged-1 Protein; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000096:biosynthesis; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000096:biosynthesis; D000072099:Serrate-Jagged Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis
chemical_list: D000951:Antigens, Neoplasm; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; C522425:MIRN34 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch; C000604408:SNAI2 protein, human; D000072099:Serrate-Jagged Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases