hsa-miR-21

breast cancer

Relationship type:

Causal

Detection method for miRNA expression:

northern blot, qRT-PCR etc

up-regulated

Validated targets of miRNA from the reference:

PDCD4

Validated targets of miRNA from TarBase:

PTEN,TPM1 : More...

Description:

The cell surface receptor tyrosine kinase HER2/neu enhances tumor metastasis. Recent studies suggest that deregulated microRNA expression promotes invasion and metastasis of cancer cells; we therefore explored the possibility that HER2/neu signaling induces the expression of specific miRNAs involved in this process. We identified a putative oncogenic miRNA, miR-21, whose expression is correlated with HER2/neu upregulation and is functionally involved in HER2/neu-induced cell invasion. We show that miR-21 is upregulated via the MAPK (ERK1/2) pathway upon stimulation of HER2/neu signaling in breast cancer cells, and over-expression of other ERK1/2 activators such as RASV12 or ID-1 is sufficient to induce miR-21 up regulation in HER2/neu negative breast cancer cells. Furthermore, the metastasis suppressor protein Programmed Cell Death 4 (PDCD4) is downregulated by miR-21 in breast cancer cells expressing HER2/neu. Our data reveal a mechanism for HER2/neu-induced cancer cell invasion via miRNA deregulation. In addition, our results identify miR-21 as a potential therapeutic target for the prevention of breast cancer invasion and metastasis.

Reference:

Up-regulation of miR-21 by HER2/neu Signaling Promotes Cell Invasion. | PMID:19419954
Huang TH, Wu F, Loeb GB, Hsu R, Heidersbach A, Brincat A, Horiuchi D, Lebbink RJ, Mo YY, Goga A, McManus MT.
J Biol Chem. 2009 Jul 3;284(27):18515-24. Epub 2009 May 6.