hsa-miR-205

breast cancer

Relationship type:

Causal

Detection method for miRNA expression:

northern blot, qRT-PCR etc

down-regulated

Validated targets of miRNA from the reference:

HER3

Validated targets of miRNA from TarBase:

unknown : More...

Description:

HER2 overexpression is a hallmark of a particularly aggressive subset of breast tumors, and its activation is strictly dependent on the trans-interaction with other members of HER family; in particular, the activation of the PI3K/Akt survival pathway, so critically important in tumorigenesis, is predominantly driven through phosphorylation of the kinase-inactive member HER3. Here, we show that miR-205, down-modulated in breast tumors compared with normal breast tissue, directly targets HER3 receptor, and inhibits the activation of the downstream mediator Akt. The reintroduction of miR-205 in SKBr3 cells inhibits their clonogenic potential and increases the responsiveness to tyrosine-kinase inhibitors Gefitinib and Lapatinib, abrogating the HER3-mediated resistance and restoring a potent proapoptotic activity. Our data describe miR-205 as a new oncosuppressor gene in breast cancer, able to interfere with the proliferative pathway mediated by HER receptor family. Our study also provides experimental evidence suggesting that miR-205 can improve the responsiveness to specific anticancer therapies.

Reference:

microRNA-205 regulates HER3 in human breast cancer. | PMID:19276373
Iorio MV, Casalini P, Piovan C, Di Leva G, Merlo A, Triulzi T, Ménard S, Croce CM, Tagliabue E.
Cancer Res. 2009 Mar 15;69(6):2195-200. Epub 2009 Mar 10.