Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: GROWTH ; LUNG-CANCER ; NF-KAPPA-B ; TRANSCRIPTION FACTOR ; mechanisms ; DUCTAL ADENOCARCINOMA ; TUMOR LYMPHANGIOGENESIS ; BREAST-CANCER METASTASIS ; HUMAN-ENDOTHELIAL-CELLS ; PROMOTES ANGIOGENESIS
    Abstract: Recent advances in cancer biology have emerged important roles for microRNAs (miRNAs) in regulating tumor responses. However, their function in mediating intercellular communication within the tumor microenvironment is thus far poorly explored. Here, we found miR-206 to be abrogated in human pancreatic ductal adenocarcinoma (PDAC) specimens and cell lines. We show that miR-206 directly targets the oncogenes KRAS and annexin a2 (ANXA2), thereby acting as tumor suppressor in PDAC cells by blocking cell cycle progression, cell proliferation, migration and invasion. Importantly, we identified miR-206 as a negative regulator of oncogenic KRAS-induced nuclear factor-kappa B transcriptional activity, resulting in a concomitant reduction of the expression and secretion of pro-angiogenic and pro-inflammatory factors including the cytokine interleukin-8, the chemokines (C-X-C motif) ligand 1 and (C-C motif) ligand 2, and the granulocyte macrophage colony-stimulating factor. We further show that miR-206 abrogates the expression and secretion of the potent pro-lymphangiogenic factor vascular endothelial growth factor C in pancreatic cancer cells through an NF-kappa B-independent mechanism. By using in vitro and in vivo approaches, we reveal that re-expression of miR-206 in PDAC cells is sufficient to inhibit tumor blood and lymphatic vessel formation, thus leading to a significant delay of tumor growth and progression. Taken together, our study sheds light onto the role of miR-206 as a pleiotropic modulator of different hallmarks of cancer, and as such raising the intriguing possibility that miR-206 may be an attractive candidate for miRNA-based anticancer therapies.
    Type of Publication: Journal article published
    PubMed ID: 25500542
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: EXPRESSION ; GROWTH ; FACTOR RECEPTOR ; ACTIVATION ; TNF-ALPHA ; TUMOR-SUPPRESSOR ; MAMMARY-GLAND DEVELOPMENT ; TRANSDUCTION PATHWAYS ; MOLECULAR PORTRAITS ; OVARIAN-TUMORS
    Abstract: Nuclear Factor kappa B (NF-kappaB) signaling is frequently deregulated in a variety of cancers and is constitutively active in estrogen receptor negative (ER-) breast cancer subtypes. These molecular subtypes of breast cancer are associated with poor overall survival. We focused on mechanisms of NF-kappaB regulation by microRNAs (miRNAs), which regulate eukaryotic gene expression at the post-transcriptional level. In a previous genome-wide miRNA screen, we had identified miR-30c-2-3p as one of the strongest negative regulators of NF-kappaB signaling. Here we have uncovered the underlying molecular mechanisms and its consequences in breast cancer. In vitro results show that miR-30c-2-3p directly targets both TNFRSF1A-associated via death domain (TRADD), an adaptor protein of the TNFR/NF-kappaB signaling pathway, and the cell cycle protein Cyclin E1 (CCNE1). Ectopic expression of miR-30c-2-3p downregulated essential cytokines IL8, IL6, CXCL1, and reduced cell proliferation as well as invasion in MDA-MB-231 breast cancer cells. RNA interference (RNAi) induced silencing of TRADD phenocopied the effects on invasion and cytokine expression caused by miR-30c-2-3p, while inhibition of CCNE1 phenocopied the effects on cell proliferation. We further confirmed the tumor suppressive role of this miRNA using a dataset of 781 breast tumors, where higher expression was associated with better survival in breast cancer patients. In summary we have elucidated the mechanism by which miR-30c-2-3p negatively regulates NF-kappaB signaling and cell cycle progression in breast cancer.
    Type of Publication: Journal article published
    PubMed ID: 25732226
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2014-10-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keklikoglou, Ioanna -- De Palma, Michele -- England -- Nature. 2014 Nov 6;515(7525):46-7. doi: 10.1038/nature13931. Epub 2014 Oct 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25337881" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/*drug therapy/*pathology ; Chemokine CCL2/*antagonists & inhibitors/*metabolism ; Female ; *Neoplasm Metastasis ; *Neovascularization, Pathologic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...