MicroRNAs are small non-coding RNA molecules that can regulate gene expression by interacting with multiple mRNAs and inducing either translation suppression or degradation of mRNA. Recently, several miRNAs were identified as either promoters or suppressors of metastasis. However, it is unclear in which step(s) of the multistep metastatic cascade these miRNAs play a defined functional role. To study the functional importance of miRNAs in epithelial-mesenchymal transition (EMT), a process thought to initiate metastasis by enhancing the motility of tumor cells, we used a well established in vitro EMT assay: transforming growth factor-beta-induced EMT in NMuMG murine mammary epithelial cells. We found that members of the miR-200 family, organized as two clusters in the genome, were repressed during EMT. Overexpression of each miRNA individually or as clusters in NMuMG cells hindered EMT by enhancing E-cadherin expression through direct targeting of ZEB1 and ZEB2, which encode transcriptional repressors of E-cadherin. In the 4TO7 mouse carcinoma cell line, which expresses low levels of endogenous E-cadherin and displays a mesenchymal phenotype, ectopic expression of the miR-200 family miRNAs significantly increased E-cadherin expression and altered cell morphology to an epithelial phenotype. Furthermore, ectopic expression of each miR-200 miRNA cluster significantly reduced the in vitro motility of 4TO7 cells in migration assays. These results suggested that loss of expression of the miR-200 family members may play a critical role in the repression of E-cadherin by ZEB1 and ZEB2 during EMT, thereby enhancing migration and invasion during cancer progression.
"In a recent study, miR-200c was shown to modulate EMT in human renal cell carcinoma . ZEB1 and ZEB2 have been identified as direct targets of the miR-200 family in several cancer cells  , and down-regulation of ZEB1 and ZEB2 increases expression of E-cadherin. In contrast, loss of miR-200, which occurs in many human cancers, results in upregulation of ZEB1/ZEB2 and suppression of E-cadherin expression  . "
"Snail factors can indeed promote the Wnt pathway (known for its regulation in selfrenewal and differentiation in stem cells) by E-Cad repression . ZEB1 and ZEB2 factors downregulate some specific members of the microRNAs 200 family (miR-200), particularly miR-200c, which targets the polycomb group member BMI1, an essential regulator of stem-cell renewal, acting as a repressor of various genes by modulating the chromatin status   . More and more reports highlight the importance of the miR-200/ZEB feedback loop in determining epithelial and mesenchymal future of tumor cells . "
[Show abstract][Hide abstract] ABSTRACT: Metastases are the hallmark of cancer. This event is in direct relationship with the ability of cancer cells to leave the tumor mass and travel long distances within the bloodstream and/or lymphatic vessels. Glioblastoma multiforme (GBM), the most frequent primary brain neoplasm, is mainly characterized by a dismal prognosis. The usual fatal issue for GBM patients is a consequence of local recurrence that is observed most of the time without any distant metastases. However, it has recently been documented that GBM cells could be isolated from the bloodstream in several studies. This observation raises the question of the possible involvement of glioblastoma-circulating cells in GBM deadly recurrence by a " homing metastasis " process. Therefore, we think it is important to review the already known molecular mechanisms underlying circulating tumor cells (CTC) specific properties, emphasizing their epithelial to mesenchymal transition (EMT) abilities and their possible involvement in tumor initiation. The idea is here to review these mechanisms and speculate on how relevant they could be applied in the forthcoming battles against GBM.
Stem cell International 04/2015; 2015. DOI:10.1155/2015/182985 · 2.81 Impact Factor
"miR-200 family is composed of five miRNAs, miR-200a, miR-200b, miR-200c, miR-141, and miR-429 (Brabletz and Brabletz, 2010). A large set of evidence has shown that the miR-200 family has several target points in ZEB1 and ZEB2 mRNAs, conversely ZEB factors bind and repress miR-200 family of miRNAs and ZEB knock-out results in an upregulation of this family of miRNAs (Christoffersen et al., 2007; Hurteau et al., 2007; Burk et al., 2008; Gregory et al., 2008; Korpal et al., 2008; Park et al., 2008). All the players identified in EMT and the mechanisms involved during embryogenesis are recapitulated during the progression of most carcinomas toward malignancy. "
Q Zhang, T Wei, K Shim, K Wright, K Xu, H L Palka-Hamblin, A Jurkevich, S Khare
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.