Paired box 6 (PAX6) is a member of the PAX family and plays an essential role in
cancer cell cycle progression, colony formation, proliferation and invasion. Its expression is upregulated in many
cancers including
breast cancer, but the process of PAX6 mRNA translation has rarely been studied. We found that PAX6 translation level increased in MCF-7
breast cancer cells treated with the chemotherapeutic
drug adriamycin (ADM), which might be attributable to
internal ribosome entry site (IRES)-mediated translation. By modifying a bicistronic
luciferase plasmid that is widely used to examine IRES activity, we found that the 469-base 5'-UTR of PAX6
mRNA contains an IRES
element and that core IRES activity is located between
nucleotides 159 and 333. Moreover, PAX6 IRES activity was induced during ADM treatment, which may be the main reason for the elevated level of
PAX6 protein. We also found that
cymarin, a
cardiac glycoside, acts as an inhibitor of
PAX6 protein expression by impairing its IRES-mediated translation. Furthermore, MCF-7 cell proliferation was suppressed during treatment with
cymarin. These results provide novel insights into the translation mechanism of PAX6 in
breast cancer cells and suggest that
cymarin is a promising candidate for the treatment of
breast cancer via targeting the expression of PAX6.