Regulation of IKKbeta by miR-199a affects NF-kappaB activity in ovarian cancer cells.
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.
Chen
R
R
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
Alvero
A B
AB
Silasi
D A
DA
Kelly
M G
MG
Fest
S
S
Visintin
I
I
Leiser
A
A
Schwartz
P E
PE
Rutherford
T
T
Mor
G
G
D001483:Base Sequence; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics*; D035683:MicroRNAs / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection; D014407:Tumor Cells, Cultured
D035683:MicroRNAs; D016328:NF-kappa B; C531408:mirn199 microRNA, human; D051550:I-kappa B Kinase