The regulation of HAS3 by miR-10b and miR-29a in neuroendocrine transdifferentiated LNCaP prostate cancer cells

Prostate cancer (PCa) is the second most common type of cancer in male worldwide. During neuroendocrine transdifferentiation (NETD), PCa cells are able to differentiate into androgen-independent neuroendocrine-like (NE-like) tumor cells, which are associated with reduced survival rates in PCa patients. The molecular processes underlying NETD have not been clarified yet, but miRNAs could play a potential role. MiRNAs are short, single-stranded, non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to the 3'-untranslated region (3'UTR) of their target mRNAs. This study aimed to explore the possible relevance and function of the transmembrane Hyaluronan Synthase 3 (HAS3) and miR-10b as well as miR-29a during NETD. Here, we validated a repression of HAS3 and an induction of miR-10b and miR-29a by quantitative real-time PCR after NETD. HAS3 was predicted as a new target gene for both miRNAs, which was verified by Reporter Gene Assays and Western Blotting. Functional analyses revealed an inhibiting effect of HAS3 on cell proliferation and migration in LNCaP cells, whereas miR-10b showed no impact. Furthermore, HAS3 increased the colony forming ability, while miR-10b diminished it. These results might give a hint on the role of miR-10b and HAS3 during NETD of PCa cells.