TWISTing stemness, inflammation and proliferation of epithelial ovarian cancer cells through MIR199A2/214.
Cancer stem cells are responsible for sustaining the tumor and giving rise to proliferating and progressively differentiating cells. However, the molecular mechanisms regulating the process of cancer stem cell (CSC) differentiation is not clearly understood. Recently, we reported the isolation of the epithelial ovarian cancer (EOC) stem cells (type I/CD44+). In this study, we show that type I/CD44+ cells are characterized by low levels of both miR-199a and miR-214, whereas mature EOC cells (type II/CD44-) have higher levels of miR-199a and miR-214. Moreover, these two micro RNAs (miRNAs) are regulated as a cluster on pri-miR-199a2 within the human Dnm3os gene (GenBank FJ623959). This study identify Twist1 as a regulator of this unique miRNA cluster responsible for the regulation of the IKKbeta/NF-kappaB and PTEN/AKT pathways and its association of ovarian CSC differentiation. Our data suggest that Twist1 may be an important regulator of 'stemness' in EOC cells. The regulation of MIR199A2/214 expression may be used as a potential therapeutic approach in EOC patients.
Yin
G
G
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
Chen
R
R
Alvero
A B
AB
Fu
H-H
HH
Holmberg
J
J
Glackin
C
C
Rutherford
T
T
Mor
G
G
D000818:Animals; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D051879:Twist-Related Protein 1 / Q000378:metabolism*
D016207:Cytokines; D018960:Hyaluronan Receptors; C547397:MIRN214 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D009687:Nuclear Proteins; D012333:RNA, Messenger; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C531408:mirn199 microRNA, human; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase; D051059:PTEN Phosphohydrolase
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