Thursday, Mar.28, 2024
miRNA:

hsa-miR-200c

Disease:

ovarian cancer (OC)

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:

TUBB3

Validated targets of miRNA from TarBase:

unknown : More...

Predicted targets: MIRANDA, TARGETSCAN, PICTAR-VERT

 

Description:

We find that miR-200c levels are high in well-differentiated endometrial, breast, and ovarian cancer cell lines, but extremely low in poorly differentiated cancer cells. Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. Microarray profiling reveals that in addition to ZEB1 and ZEB2, other mesenchymal genes (such as FN1, NTRK2, and QKI), which are also predicted direct targets of miR-200c, are indeed inhibited by addition of exogenous miR-200c. One such gene, class III beta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. This finding is of particular significance because we show that restoration of miR-200c increases sensitivity to microtubule-targeting agents by 85%. Because expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3. Because miR-200c is crucial for maintenance of epithelial identity, behavior, and sensitivity to chemotherapy, we propose that it warrants further investigation as a therapeutic strategy for aggressive, drug-resistant cancers.

 

 

Reference:

MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents. | PMID:19435871
Cochrane DR, Spoelstra NS, Howe EN, Nordeen SK, Richer JK.
Mol Cancer Ther. 2009 May 12. [Epub ahead of print]

 

 
 
 
  miRBase
  Tarbase
  miRGen
  miRGator
  CCBB
  MicroRNA.org
  miRRim
  miRNAMap 2.0
 
 
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