title: miR-29b defines the pro-/anti-proliferative effects of S100A7 in breast cancer.
abstract: BACKGROUND
  S100A7 (Psoriasin) is an inflammatory protein known to be upregulated in breast cancer. However, the role of S100A7 in breast cancer has been elusive, since both pro- and anti-proliferative roles have been reported in different types of breast cancer cells and animal models. To date, the mechanism by which S100A7 differentially regulates breast cancer cell proliferation is still not clear.
  
  
  METHODS
  We used Gene Functional Enrichment Analysis to search for the determining factor of S100A7 differential regulation. We confirmed the factor and elaborated its regulating mechanism using in vitro cell culture. We further verified the findings using xenografts of human breast cancer cells in nude mice.
  
  
  RESULTS
  In the present study, we show that S100A7 significantly upregulates the expression of miR-29b in Estrogen Receptor (ER)-positive breast cancer cells (represented by MCF7), and significantly downregulates miR-29b in ER-negative cells (represented by MDA-MB-231) [Corrected]. The differential regulation of miR-29b by S100A7 in ER-positive and ER-negative breast cancer is supported by the gene expression analysis of TCGA invasive breast cancer dataset. miR-29b transcription is inhibited by NF-κB, and NF-κB activation is differentially regulated by S100A7 in ER-positive and ER-negative breast cancer cells. This further leads to differential regulation of PI3K p85α and CDC42 expression, p53 activation and p53-associated anti-proliferative pathways. Reversing the S100A7-caused changes of miR-29b expression by transfecting exogenous miR-29b or miR-29b-Decoy can inhibit the effects of S100A7 on in vitro cell proliferation and tumor growth in nude mice.
  
  
  CONCLUSIONS
  The distinct modulations of the NF-κB - miR-29b - p53 pathway make S100A7 an oncogene in ER-negative and a cancer-suppressing gene in ER-positive breast cancer cells, with miR-29b being the determining regulatory factor.
authors.affiliation: Department of Pathology, The Ohio State University Wexner Medical Center, 840 BRT, 460W 12th Ave, Columbus, OH, 43210, USA. zhao.364@osu.edu.
authors.forename: Helong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Pathology, The Ohio State University Wexner Medical Center, 840 BRT, 460W 12th Ave, Columbus, OH, 43210, USA. wilkie.20@osu.edu.
authors.forename: Tasha
authors.initials: T
authors.lastname: Wilkie
authors.affiliation: Department of Pathology, The Ohio State University Wexner Medical Center, 840 BRT, 460W 12th Ave, Columbus, OH, 43210, USA. yadwinder.deol@osumc.edu.
authors.forename: Yadwinder
authors.initials: Y
authors.lastname: Deol
authors.affiliation: Department of Pathology, The Ohio State University Wexner Medical Center, 840 BRT, 460W 12th Ave, Columbus, OH, 43210, USA. amita.sneh@osumc.edu.
authors.forename: Amita
authors.initials: A
authors.lastname: Sneh
authors.affiliation: Department of Pathology, The Ohio State University Wexner Medical Center, 840 BRT, 460W 12th Ave, Columbus, OH, 43210, USA. akaansha.ganju@osumc.edu.
authors.forename: Akaansha
authors.initials: A
authors.lastname: Ganju
authors.affiliation: Department of Pathology, The Ohio State University Wexner Medical Center, 840 BRT, 460W 12th Ave, Columbus, OH, 43210, USA. basree.1@osu.edu.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Basree
authors.affiliation: Department of Pathology, The Ohio State University Wexner Medical Center, 840 BRT, 460W 12th Ave, Columbus, OH, 43210, USA. Mohd.Nasser@osumc.edu.
authors.forename: Mohd W
authors.initials: MW
authors.lastname: Nasser
authors.affiliation: Department of Pathology, The Ohio State University Wexner Medical Center, 840 BRT, 460W 12th Ave, Columbus, OH, 43210, USA. Ramesh.Ganju@osumc.edu.
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ganju
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D020764:cdc42 GTP-Binding Protein / Q000235:genetics
chemical_list: D035683:MicroRNAs; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D016159:Tumor Suppressor Protein p53; D020764:cdc42 GTP-Binding Protein; C532045:MIRN29a microRNA, human; C089242:S100A7 protein, human