title: The RNA-binding protein Musashi 1 stabilizes the oncotachykinin 1 mRNA in breast cancer cells to promote cell growth.
abstract: Substance P and its truncated receptor exert oncogenic effects. The high production of substance P in breast cancer cells (BCCs) is caused by the enhancement of tachykinin (TAC)1 translation by cytosolic factor. In vitro translational studies and mRNA stabilization analyses indicate that BCCs contain the factor needed to increase TAC1 translation and to stabilize the mRNA. Prediction of protein folding, RNA-shift analysis, and proteomic analysis identified a 40 kDa molecule that interacts with the noncoding exon 7. Western blot analysis and RNA supershift identified Musashi 1 (Msi1) as the binding protein. Ectopic expression of TAC1 in nontumorigenic breast cells (BCs) indicates that TAC1 regulates its stability by increasing Msi1. Using a reporter gene system, we showed that Msi1 competes with microRNA (miR)130a and -206 for the 3' UTR of exon 7/TAC1. In the absence of Msi1 and miR130a and -206, reporter gene activity decreased, indicating that Msi1 expression limits TAC1 expression. Tumor growth was significantly decreased when nude BALB/c mice were injected with Msi1-knockdown BCCs. In summary, the RNA-binding protein Msi1 competes with miR130a and -206 for interaction with TAC1 mRNA, to stabilize and increase its translation. Consequently, these interactions increase tumor growth.
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: George R
authors.initials: GR
authors.lastname: Nahas
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Raghav G
authors.initials: RG
authors.lastname: Murthy
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Shyam A
authors.initials: SA
authors.lastname: Patel
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Teja
authors.initials: T
authors.lastname: Ganta
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Greco
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA rameshwa@njms.rutgers.edu.
authors.forename: Pranela
authors.initials: P
authors.lastname: Rameshwar
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics*; D016923:Cell Death / Q000235:genetics*; D045744:Cell Line, Tumor / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000235:genetics*; D040901:Proteomics / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: C104786:Msi1h protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins
keywords: REST; cancer stem cell; miRNA; neurokinin-1; substance P