TWISTing stemness, inflammation and proliferation of epithelial ovarian cancer cells through MIR199A2/214

Abstract

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 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 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 IKKβ/NFκB and PTEN/AKT pathways and its association of ovarian cancer stem cell 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.

PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

“…These aberrantly expressed miRNAs play essential roles in the regulation of TIC properties as either TIC suppressors or promoters [20][21][22][23][24] . Moreover, a series of critical signalling pathways involved in the regulation of TIC properties have been uncovered with the identification of the targets of these miRNAs 19,[25][26][27][28] . Importantly, miRNAs are also demonstrated to be promising biomarkers and amenable therapeutic targets 5,19,24 .…”

Restoration of microRNA-214 expression reduces growth of myeloma cells through positive regulation of P53 and inhibition of DNA replication

“…Over-expression of miR-214 has been reported in several tumors, such as melanoma, ovarian cancer and gastric cancer. [7][8][9] In contrast, miR-214 was found to be down-regulated in breast cancer, resulting in increased cell proliferation and invasion. 10 Likewise, low miR-214 expression levels were associated with metastasis and invasion of cervical tumors 11 and it has also been recently described that miR-214 is down-regulated in primary central nervous system lymphomas.…”

TRX-E-002-1 Induces c-Jun–Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo

“…These patient samples were obtained from patients at Yale New Haven Hospital (New Haven, CT) who were diagnosed with stage III/IV serous ovarian cancer and propagated as described previously (9,10,14,(28)(29)(30)(31)(32)(33) …”