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Thursday, Mar.28, 2024
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miRNA: |
hsa-miR-205 |
Disease: |
squamous carcinoma |
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: |
SHIP2 |
Validated targets of miRNA from TarBase: |
unknown : More... |
Predicted targets: |
MIRANDA, TARGETSCAN, PICTAR-VERT |
Description: Here we demonstrate not only that the lipid phosphatase SHIP2 is a target of miRNA-205 (miR-205) in epithelial cells, but, more importantly, that the corneal epithelial-specific miR-184 can interfere with the ability of miR-205 to suppress SHIP2 levels. This is the first example of a miRNA negatively regulating another to maintain levels of a target protein. Interfering with miR-205 function by using a synthetic antagomir, or by the ectopic expression of miR-184, leads to a coordinated damping of the Akt signaling pathway via SHIP2 induction. This was associated with a marked increase in keratinocyte apoptosis and cell death. Aggressive squamous cell carcinoma (SCC) cells exhibited elevated levels of miR-205. This was associated with a concomitant reduction in SHIP2 levels. Partial knockdown of endogenous miR-205 in SCCs markedly decreased phosphorylated Akt and phosphorylated BAD levels and increased apoptosis. We were able to increase SHIP2 levels in SCC cells after inhibition of miR-205. Therefore, miR-205 might have diagnostic value in determining the aggressivity of SCCs. Blockage of miR-205 activity with an antagomir or via ectopic expression of miR-184 could be novel therapeutic approaches for treating aggressive SCCs.
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Reference:
MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia. | PMID:19033458
Yu J, Ryan DG, Getsios S, Oliveira-Fernandes M, Fatima A, Lavker RM.
Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19300-5. Epub 2008 Nov 25. |
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