Exploring PTEN-derived Noncoding RNA’s Function in Breast Cancer

In breast cancer, a common alteration involves the inactivation of the tumor suppressor gene PTEN. PTEN typically prevents the overstimulation of the AKT pathway, slowing cell proliferation. While the mechanisms by which PTEN is reduced are understood in some breast cancer cases, others show unexplained PTEN reduction. We previously investigated a post-transcriptional mechanism involving the splicing of PTEN's first intron, which is a minor intron. Our data showed that the unspliced minor intron is cleaved and polyadenylated, forming a long non-coding RNA (lncRNA) that acts independently from the PTEN protein. Preliminary data also showed that this lncRNA affects cell proliferation and migration. We aimed to understand the functional mechanisms of this lncRNA through several phenotypic studies after overexpressing the lncRNA into breast cancer cell lines. Additionally, we aimed to confirm whether this lncRNA functions via micro-RNA sequestering and whether blocking the binding of the lncRNA to the microRNA will alter its cellular behavior. To verify whether the lncRNA is indeed responsible for changing cellular behavior, we determined the site of lncRNA formation to assess its potential as a target for intervention. Our data suggests that this novel lncRNA has a crucial role in regulating breast cancer cell proliferation and thus could be targeted therapeutically.