hsa-miR-221

breast cancer

Relationship type:

Unspecified

Detection method for miRNA expression:

Northern blot, qRT-PCR etc

up-regulated

Validated targets of miRNA from the reference:

p27(Kip1)

Validated targets of miRNA from TarBase:

KIT : More...

Description:

The expression of miR-221 and miR-222 was also significantly (2-fold) elevated in HER2/neu-positive primary human breast cancer tissues that are known to be resistant to endocrine therapy compared with HER2/neu-negative tissue samples. Ectopic expression of miR-221/222 rendered the parental MCF-7 cells resistant to tamoxifen. The protein level of the cell cycle inhibitor p27(Kip1), a known target of miR-221/222, was reduced by 50% in OHT(R) cells and by 28-50% in miR-221/222-overexpressing MCF-7 cells. Furthermore, overexpression of p27(Kip1) in the resistant OHT(R) cells caused enhanced cell death when exposed to tamoxifen. This is the first study demonstrating a relationship between miR-221/222 expression and HER2/neu overexpression in primary breast tumors that are generally resistant to tamoxifen therapy. This finding also provides the rationale for the application of altered expression of specific miRNAs as a predictive tamoxifen-resistant breast cancer marker.

Reference:

MicroRNA-221/222 Confers Tamoxifen Resistance in Breast Cancer by Targeting p27Kip1. | PMID:18708351
Miller TE, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro CL, Jacob S, Majumder S.
J Biol Chem. 2008 Oct 31;283(44):29897-903. Epub 2008 Aug 15.