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PMID: 18408758 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Regulation of IKKbeta by miR-199a affects NF-kappaB activity in ovarian cancer cells.

Oncogene ·Vol. 27 ·No. 34 ·2008-08-07 ·Pages 4712-23

Chen R, Alvero AB, Silasi DA, Kelly MG, Fest S, Visintin I, Leiser A, Schwartz PE, Rutherford T, Mor G

Abstract

Cancer progression is an abnormal form of tissue repair characterized by chronic inflammation. IkappaB kinase-beta (IKKbeta) required for nuclear factor-kappaB (NF-kappaB) activation plays a critical role in this process. Using EOC cells isolated from malignant ovarian cancer ascites and solid tumors, we identified IKKbeta as a major factor promoting a functional TLR-MyD88-NF-kappaB pathway that confers to EOC cell the capacity to constitutively secrete proinflammatory/protumor cytokines and therefore promoting tumor progression and chemoresistance. Furthermore, we describe for the first time the identification of the microRNA hsa-miR-199a as a regulator of IKKbeta expression. Our study describes the property of ovarian cancer cells to enhance the inflammatory microenvironment as a result of the expression of an active IKKbeta pathway. Identification of these markers in patients' tumor samples may facilitate the adequate selection of treatment and open new venues for the development of effective therapy for chemoresistant ovarian cancers.

MeSH Terms
Base Sequence Female Gene Expression Regulation, Neoplastic Humans I-kappa B Kinase/genetics MicroRNAs/physiology Models, Biological Molecular Sequence Data NF-kappa B/metabolism Ovarian Neoplasms/genetics,metabolism Sequence Homology, Nucleic Acid Transfection Tumor Cells, Cultured
Chemicals
MicroRNAs NF-kappa B mirn199 microRNA, human I-kappa B Kinase
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Chen R
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
Alvero A B
Silasi D A
Kelly M G
Fest S
Visintin I
Leiser A
Schwartz P E
Rutherford T
Mor G
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Article Info
Journal
Oncogene
Abbr.
Oncogene
ISSN
1476-5594
DOI
10.1038/onc.2008.112
Published
2008-08-07
Epub
2008-00-14
Pages
4712-23
Language
English
Region
England
NLM ID
8711562
PMCID
PMC3041589
Subset
IM
Grants
NCI NIH HHS · R01 CA127913-02 · United States
NCI NIH HHS · R01 CA118678 · United States
NCI NIH HHS · R01 CA118678-02 · United States
NCI NIH HHS · R01 CA127913 · United States
NCI NIH HHS · R01 CA127913-01A2 · United States
External Links
PubMed source DOI: 10.1038/onc.2008.112 PMC Full Text View journal details
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