hsa-miR-126

colorectal cancer

Relationship type:

Causal

Detection method for miRNA expression:

Northern blot, qRT-PCR etc

down-regulated

Validated targets of miRNA from the reference:

p85beta

Validated targets of miRNA from TarBase:

unknown : More...

Description:

Using micro(RNA) arrays, we found a ubiquitous loss of miR-126 expression in colon cancer lines when compared to normal human colon epithelia. Reconstitution of miR-126 in colon cancer cells resulted in a significant growth reduction as evidenced in clonogenic assays. A search for miR-126 gene targets revealed p85beta, a regulatory subunit involved in stabilizing and propagating the phosphatidylinositol 3-kinase (PI3K) signal. Additionally, using reporter constructs, we show that the p85beta-3' untranslated region is directly targeted by miR-126. Furthermore, this miR-126 mediated reduction of p85beta was accompanied by a substantial reduction in phosphorylated AKT levels in the cancer cells, suggesting an impairment in PI3K signaling. Finally, in a panel of matched normal colon and primary colon tumors, each of the tumors demonstrated miR-126 down-regulation together with an increase in the p85beta protein level. Taken together, we propose that miR-126 regulates PI3K signaling partly by targeting p85beta, and that the loss of miR-126 may provide a selective growth advantage during colon carcinogenesis.

Reference:

The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers. | PMID:18663744
Guo C, Sah JF, Beard L, Willson JK, Markowitz SD, Guda K.
Genes Chromosomes Cancer. 2008 Nov;47(11):939-46.