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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

The ZEB/miR-200 network and the p53 family members.
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fig4: The ZEB/miR-200 network and the p53 family members.

Mentions: The p53 transcription factor can induce or repress a large set of genes and miRNAs [129, 130]. The p53 and its homologs p63 and p73 are well involved in tumor metastasis and tumor progression [131–133]. The p63 and p73 members exist as full-size proteins (TAp63 and TAp73) or truncated forms (ΔNp63 and ΔNp73) that lack the transcriptional activation domain. In early studies, it was demonstrated that ΔNp63/73 expression is directly repressed by ZEB binding, establishing a link between the ZEB proteins and the p53 family. In addition, TAp73 isoforms were also found to be repressed to a lesser extent during myoblast differentiation and in mouse embryonic fibroblasts (MEFs) [134] (Figure 4).


The Regulatory Role of MicroRNAs in EMT and Cancer.

Zaravinos A - J Oncol (2015)

The ZEB/miR-200 network and the p53 family members.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: The ZEB/miR-200 network and the p53 family members.
Mentions: The p53 transcription factor can induce or repress a large set of genes and miRNAs [129, 130]. The p53 and its homologs p63 and p73 are well involved in tumor metastasis and tumor progression [131–133]. The p63 and p73 members exist as full-size proteins (TAp63 and TAp73) or truncated forms (ΔNp63 and ΔNp73) that lack the transcriptional activation domain. In early studies, it was demonstrated that ΔNp63/73 expression is directly repressed by ZEB binding, establishing a link between the ZEB proteins and the p53 family. In addition, TAp73 isoforms were also found to be repressed to a lesser extent during myoblast differentiation and in mouse embryonic fibroblasts (MEFs) [134] (Figure 4).

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