hsa-miR-146a

ovarian cancer (OC)

Relationship type:

Causal

Detection method for miRNA expression:

Northern blot, qRT-PCR etc

up-regulated

Validated targets of miRNA from the reference:

BRCA1, BRCA2

Validated targets of miRNA from TarBase:

unknown : More...

Description:

A G to C polymorphism (rs2910164) is located within the sequence of miR-146a precursor, which leads to a change from a G:U pair to a C:U mismatch in its stem region. The predicted miR-146a target genes include BRCA1 and BRCA2, which are key breast and ovarian cancer genes. we studied associations between this polymorphism and age of diagnosis in 42 patients with familial breast cancer and 82 patients with familial ovarian cancer. Breast cancer patients who had at least one miR-146a variant allele were diagnosed at an earlier age than with no variant alleles (Median age: 45 vs 56, p=0.029) and ovarian cancer patients who had at least one miR-146a variant allele were diagnosed younger than women without any variant allele (Median age: 45 vs 50, p=0.014). in a target in vitro assay we observed that miR-146a could bind to the 3'UTRs of BRCA1 and BRCA2 mRNAs and potentially modulate their mRNA expression. Intriguingly, the binding capacity between the 3'UTR of BRCA1 and miR-146a were statistically significantly stronger in variant C-allele than those in common G-allele (p=0.046). Taken together, our data suggest that breast/ovarian cancer patients with variant C-allele miR-146a may have high levels of mature miR-146 and that these variants predispose them to an earlier age of onset of familial breast and ovarian cancer.

Reference:

A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. | PMID:18660546
Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB, Zhao H.
Carcinogenesis. 2008 Oct;29(10):1963-6. Epub 2008 Jul 27.