22
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA.

      Molecular and Cellular Biology

      Animals, Base Sequence, Breast Neoplasms, genetics, metabolism, pathology, Cell Line, Cell Movement, physiology, Epithelial Cells, cytology, Female, Gene Expression Profiling, Humans, Mice, MicroRNAs, Microarray Analysis, Molecular Sequence Data, Neoplasm Invasiveness, Sequence Alignment, Signal Transduction, Smad4 Protein, Transcription, Genetic, Transforming Growth Factor beta, rhoA GTP-Binding Protein

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Transforming growth factor beta (TGF-beta) signaling facilitates metastasis in advanced malignancy. While a number of protein-encoding genes are known to be involved in this process, information on the role of microRNAs (miRNAs) in TGF-beta-induced cell migration and invasion is still limited. By hybridizing a 515-miRNA oligonucleotide-based microarray library, a total of 28 miRNAs were found to be significantly deregulated in TGF-beta-treated normal murine mammary gland (NMuMG) epithelial cells but not Smad4 knockdown NMuMG cells. Among upregulated miRNAs, miR-155 was the most significantly elevated miRNA. TGF-beta induces miR-155 expression and promoter activity through Smad4. The knockdown of miR-155 suppressed TGF-beta-induced epithelial-mesenchymal transition (EMT) and tight junction dissolution, as well as cell migration and invasion. Further, the ectopic expression of miR-155 reduced RhoA protein and disrupted tight junction formation. Reintroducing RhoA cDNA without the 3' untranslated region largely reversed the phenotype induced by miR-155 and TGF-beta. In addition, elevated levels of miR-155 were frequently detected in invasive breast cancer tissues. These data suggest that miR-155 may play an important role in TGF-beta-induced EMT and cell migration and invasion by targeting RhoA and indicate that it is a potential therapeutic target for breast cancer intervention.

          Related collections

          Author and article information

          Journal
          18794355
          2573297
          10.1128/MCB.00941-08

          Comments

          Comment on this article