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MicroRNA-206 functi...
MicroRNA-206 functions as a pleiotropic modulator of cell proliferation, invasion and lymphangiogenesis in pancreatic adenocarcinoma by targeting ANXA2 and KRAS genes
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- Keklikoglou, I. (författare)
- German Cancer Research Centre, Germany; Swiss Federal Institute Technology Lausanne EPFL, Switzerland
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- Hosaka, K. (författare)
- Karolinska Institutet,Karolinska Institute, Sweden
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- Bender, C. (författare)
- German Cancer Research Centre, Germany
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- Bott, A. (författare)
- German Cancer Research Centre, Germany
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- Koerner, C. (författare)
- German Cancer Research Centre, Germany
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- Mitra, D. (författare)
- German Cancer Research Centre, Germany
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- Will, R. (författare)
- German Cancer Research Centre, Germany
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- Woerner, A. (författare)
- German Cancer Research Centre, Germany
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- Muenstermann, E. (författare)
- German Cancer Research Centre, Germany
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- Wilhelm, H. (författare)
- German Cancer Research Centre, Germany
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- Cao, Yihai (författare)
- Karolinska Institutet,Linköpings universitet,Avdelningen för kardiovaskulär medicin,Medicinska fakulteten,Karolinska Institute, Sweden; University of Leicester, England; Glenfield Hospital, England
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- Wiemann, S. (författare)
- German Cancer Research Centre, Germany
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(creator_code:org_t)
- 2014-12-15
- 2015
- Engelska.
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Ingår i: Oncogene. - : NATURE PUBLISHING GROUP. - 0950-9232 .- 1476-5594. ; 34:37, s. 4867-4878
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https://liu.diva-por... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
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Oncogene
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Till lärosätets databas
- Av författaren/redakt...
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Keklikoglou, I.
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Hosaka, K.
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Bender, C.
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Bott, A.
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Koerner, C.
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Mitra, D.
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visa fler...
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Will, R.
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Woerner, A.
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Muenstermann, E.
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Wilhelm, H.
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Cao, Yihai
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Wiemann, S.
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
- Artiklar i publikationen
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Oncogene
- Av lärosätet
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Linköpings universitet
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Karolinska Institutet