Article

miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis.

IMBA Vienna, Institute for Molecular Pathology, Dr Bohrgasse 3-5, 1030 Vienna, Austria.
EMBO Reports (Impact Factor: 7.86). 03/2009; 10(4):400-5. DOI: 10.1038/embor.2009.9
Source: PubMed

ABSTRACT Several microRNAs (miRNAs) have recently been described as crucial regulators of epithelial-to-mesenchymal transition (EMT) and metastasis. By comparing the expression profiles of miRNAs, we found upregulation of miR-29a in mesenchymal, metastatic RasXT cells relative to epithelial EpRas cells. Overexpression of miR-29a suppressed the expression of tristetraprolin (TTP), a protein involved in the degradation of messenger RNAs with AU-rich 3'-untranslated regions, and led to EMT and metastasis in cooperation with oncogenic Ras signalling. We also observed enhanced miR-29a and reduced TTP levels in breast cancer patient samples, indicating relevance for human disease. Previously, miR-29 family members were shown to have tumour-suppressive effects in haematopoietic, cholangiocytic and lung tumours. Therefore, miRNAs can act as either oncogenes or tumour suppressors, depending on the context.

1 Follower
 · 
94 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Clinical treatment with glucocorticoids (GC) can be complicated by cytokine-induced glucocorticoid low-responsiveness (GC-resistance, GCR), a condition associated with a homogeneous reduction in the expression of GC-receptor- (GR-) driven anti-inflammatory genes. However, GR level and phosphorylation changes modify the expression of individual GR-responsive genes differently. As sustained IL-1β exposure is key in the pathogenesis of several major diseases with prevalent GCR, we examined GR signaling and the mRNA expression of six GR-driven genes in cells cultured in IL-1β and afterwards challenged with GC. After a GC challenge, sustained IL-1β exposure reduced the cytoplasmic GR level, and phosphorylation, and GR nuclear translocation and led to selective GCR in the expression of the studied genes. Compared to GC alone, in a broad range of GC doses plus sustained IL-1β, FKBP51 mRNA expression was reduced by 1/3, TTP by 2/3, and IRF8 was completely knocked down. In contrast, high GC doses did not change the expression of GILZ and DUSP1, while IGFBP1 was increased by 5-fold. These effects were cytokine-selective, IL-1β dose- and IL-1R1-dependent. The integrated gain and loss of gene functions in the “split GCR” model may provide target cells with a survival advantage by conferring resistance to apoptosis, chemotherapy, and GC.
    Mediators of Inflammation 01/2015; 2015:1-16. DOI:10.1155/2015/347965 · 2.42 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In recent years, there has been a tremendous and growing interest among researchers to investigate the role of mircoRNA (miRNA) in normal cellular as well as in disease processes. miRNAs are a family of small non-coding RNAs which were reported to regulate the expression of various oncogenes or tumor suppressor genes. The expression profiling of miRNAs has already entered into cancer clinics as diagnostic and prognostic biomarkers to assess tumor initiation, progression and response to treatment in cancer patients. This review summarizes: (i) the current understanding of interactions between miRNAs and their target genes, (ii) recent advances in the regulatory mechanisms that control the expression of genes related to carcinogenesis, and (iii) the role of miRNAs in cancer diagnosis and therapy.
    Cancer Cell International 04/2015; 15(1). DOI:10.1186/s12935-015-0185-1 · 1.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pancreatic ductal adenocarcinoma is an aggressive malignancy with late presentation, metastatic potential and very poor prognosis. Therefore, there is an urgent need for novel diagnostic and prognostic biomarkers. MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. Altered expression of microRNAs has been reported in wide range of malignancies, including pancreatic ductal adenocarcinoma. The aim of this study was to analyze the expression of selected microRNAs in normal pancreas, chronic pancreatitis and pancreatic ductal adenocarcinoma tissues and evaluate their diagnostic and prognostic potential. Using quantitative real-time PCR, expression levels of 4 microRNAs were examined in 74 tumor tissues, 18 tissues of chronic pancreatitis and 9 adjacent normal tissues and correlated with clinicopathological features of patients. Expression levels of miR-21, miR-34a and miR-198 were significantly higher, whereas levels of miR-217 were significantly lower in pancreatic ductal adenocarcinomas compared to healthy tissues and tissues of chronic pancreatitis. Moreover, increased expression of miR-21 and miR-198 was significantly associated with shorter disease free survival and overall survival. Our data suggest that altered expression of examined microRNAs is related to neoplastic transformation and progression of the disease and these microRNAs could serve as diagnostic and prognostic biomarkers for pancreatic ductal adenocarcinoma. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1373952531543898.
    Diagnostic Pathology 04/2015; 10(1):38. DOI:10.1186/s13000-015-0272-6 · 2.41 Impact Factor

Preview

Download
4 Downloads
Available from