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The Regulatory Role of MicroRNAs in EMT and Cancer.

Zaravinos A - J Oncol (2015)

Bottom Line: The aberrant expression of the miR-200 family in cancer and its involvement in the initiation and progression of malignant transformation has been well demonstrated.The ability of the autocrine TGF-β/ZEB/miR-200 signaling regulatory network to control cell plasticity between the epithelial and mesenchymal state is further discussed.Various miRNAs are reported to directly target EMT transcription factors and components of the cell architecture, as well as miRNAs that are able to reverse the EMT process by targeting the Notch and Wnt signaling pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Karolinska Institutet Huddinge, 171 77 Stockholm, Sweden.

ABSTRACT
The epithelial to mesenchymal transition (EMT) is a powerful process in tumor invasion, metastasis, and tumorigenesis and describes the molecular reprogramming and phenotypic changes that are characterized by a transition from polarized immotile epithelial cells to motile mesenchymal cells. It is now well known that miRNAs are important regulators of malignant transformation and metastasis. The aberrant expression of the miR-200 family in cancer and its involvement in the initiation and progression of malignant transformation has been well demonstrated. The metastasis suppressive role of the miR-200 members is strongly associated with a pathologic EMT. This review describes the most recent advances regarding the influence of miRNAs in EMT and the control they exert in major signaling pathways in various cancers. The ability of the autocrine TGF-β/ZEB/miR-200 signaling regulatory network to control cell plasticity between the epithelial and mesenchymal state is further discussed. Various miRNAs are reported to directly target EMT transcription factors and components of the cell architecture, as well as miRNAs that are able to reverse the EMT process by targeting the Notch and Wnt signaling pathways. The link between cancer stem cells and EMT is also reported and the most recent developments regarding clinical trials that are currently using anti-miRNA constructs are further discussed.

No MeSH data available.


Related in: MedlinePlus

Regulation of the Notch and Wnt signaling pathways by miR-200.
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Related In: Results  -  Collection


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fig3: Regulation of the Notch and Wnt signaling pathways by miR-200.

Mentions: Furthermore, a functional link was recently established between the canonical Wnt pathway and ZEB1, demonstrating that ZEB1 is a direct transcriptional target of β-catenin in colon cancer cells [126, 127]. However, the ZEB2/Wnt relationship in colon cancer yet remains unclear. Wnt signaling is also connected with the ZEB/miR-200 network in cancer. miR-200a was reported to downregulate β-catenin-mediated transcription via targeting either ZEB or β-catenin, thus downregulating the activation of Wnt/β-catenin signaling [128] (Figure 3). In contrast, miR-200b and miR-200c have no effect on β-catenin.


The Regulatory Role of MicroRNAs in EMT and Cancer.

Zaravinos A - J Oncol (2015)

Regulation of the Notch and Wnt signaling pathways by miR-200.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4389820&req=5

fig3: Regulation of the Notch and Wnt signaling pathways by miR-200.
Mentions: Furthermore, a functional link was recently established between the canonical Wnt pathway and ZEB1, demonstrating that ZEB1 is a direct transcriptional target of β-catenin in colon cancer cells [126, 127]. However, the ZEB2/Wnt relationship in colon cancer yet remains unclear. Wnt signaling is also connected with the ZEB/miR-200 network in cancer. miR-200a was reported to downregulate β-catenin-mediated transcription via targeting either ZEB or β-catenin, thus downregulating the activation of Wnt/β-catenin signaling [128] (Figure 3). In contrast, miR-200b and miR-200c have no effect on β-catenin.

Bottom Line: The aberrant expression of the miR-200 family in cancer and its involvement in the initiation and progression of malignant transformation has been well demonstrated.The ability of the autocrine TGF-β/ZEB/miR-200 signaling regulatory network to control cell plasticity between the epithelial and mesenchymal state is further discussed.Various miRNAs are reported to directly target EMT transcription factors and components of the cell architecture, as well as miRNAs that are able to reverse the EMT process by targeting the Notch and Wnt signaling pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Karolinska Institutet Huddinge, 171 77 Stockholm, Sweden.

ABSTRACT
The epithelial to mesenchymal transition (EMT) is a powerful process in tumor invasion, metastasis, and tumorigenesis and describes the molecular reprogramming and phenotypic changes that are characterized by a transition from polarized immotile epithelial cells to motile mesenchymal cells. It is now well known that miRNAs are important regulators of malignant transformation and metastasis. The aberrant expression of the miR-200 family in cancer and its involvement in the initiation and progression of malignant transformation has been well demonstrated. The metastasis suppressive role of the miR-200 members is strongly associated with a pathologic EMT. This review describes the most recent advances regarding the influence of miRNAs in EMT and the control they exert in major signaling pathways in various cancers. The ability of the autocrine TGF-β/ZEB/miR-200 signaling regulatory network to control cell plasticity between the epithelial and mesenchymal state is further discussed. Various miRNAs are reported to directly target EMT transcription factors and components of the cell architecture, as well as miRNAs that are able to reverse the EMT process by targeting the Notch and Wnt signaling pathways. The link between cancer stem cells and EMT is also reported and the most recent developments regarding clinical trials that are currently using anti-miRNA constructs are further discussed.

No MeSH data available.


Related in: MedlinePlus