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Thursday, May.2, 2024
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miRNA: |
hsa-miR-155 |
Disease: |
breast cancer |
Relationship type: |
Causal |
Detection method for miRNA expression: |
Northern blot, qRT-PCR etc |
Expression pattern of miRNA: |
up-regulated |
Validated targets of miRNA from the reference: |
RhoA |
Validated targets of miRNA from TarBase: |
AGTR1 : More... |
Predicted targets: |
MIRANDA, TARGETSCAN, PICTAR-VERT |
Description: Transforming growth factor beta (TGF-beta) signaling facilitates metastasis in advanced malignancy. While a number of protein-encoding genes are known to be involved in this process, information on the role of microRNAs (miRNAs) in TGF-beta-induced cell migration and invasion is still limited. By hybridizing a 515-miRNA oligonucleotide-based microarray library, a total of 28 miRNAs were found to be significantly deregulated in TGF-beta-treated normal murine mammary gland (NMuMG) epithelial cells but not Smad4 knockdown NMuMG cells. Among upregulated miRNAs, miR-155 was the most significantly elevated miRNA. TGF-beta induces miR-155 expression and promoter activity through Smad4. The knockdown of miR-155 suppressed TGF-beta-induced epithelial-mesenchymal transition (EMT) and tight junction dissolution, as well as cell migration and invasion. Further, the ectopic expression of miR-155 reduced RhoA protein and disrupted tight junction formation. Reintroducing RhoA cDNA without the 3' untranslated region largely reversed the phenotype induced by miR-155 and TGF-beta. In addition, elevated levels of miR-155 were frequently detected in invasive breast cancer tissues. These data suggest that miR-155 may play an important role in TGF-beta-induced EMT and cell migration and invasion by targeting RhoA and indicate that it is a potential therapeutic target for breast cancer intervention.
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Reference:
MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. | PMID:18794355
Kong W, Yang H, He L, Zhao JJ, Coppola D, Dalton WS, Cheng JQ.
Mol Cell Biol. 2008 Nov;28(22):6773-84. Epub 2008 Sep 15. |
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