TRANSCRIPTIONAL REGULATION OF MYOSIN1C ISOFORM A IN THE PROSTATE CANCER CELL LINES
MetadataShow full item record
AbstractThe metastasis of prostate cancer (PCa) cells is a major reason for the PCa-related death. For this reason, it is of paramount importance to uncover mechanisms that cause the metastatic processes in PCa and target them for therapeutic purposes. Recent studies have showed that the expression of Myosin1C-isoform A is increased in PCa and the differential expression of Myosin1C-isoform A is observed in different metastatic prostate cancer cells. For example, PC3 cells express Myosin1C-isoform A more than the metastatic PCa cell line, LNCaP. Also, it is found that functionally this protein increases invasion of PCa cells. Despite the accumulating information about Myosin1C-isoform A, not enough is yet known about which gene regulatory mechanisms control the expression of Myosin1C-isoform A in normal prostate and during PCa progression. Therefore, my aim was to identify transcriptional mechanisms that can regulate the expression of Myosin1C-isoform A in two different metastatic PCa cell lines, LNCaP and PC3. Specifically, I conducted experiments to find whether Androgen receptor and epigenetic factors have an influence on the expression of Myosin1C-isoform A. My experiments showed that Androgen receptor can repress the expression of Myosin1C-isoform A in LNCaP cells, but not in PC3 cells. The repressive effect of the Androgen receptor in LNCaP cells occurs without its binding to the upstream gene regulatory region of Myosin1C-isoform A. Bioinformatic analysis of the chromatin landscape and DNA methylation profile around the promoter of Myosin1C-isoform A showed that this promoter has a more transcription-repressive environment in LNCaP cells than in PC3 cells. Increasing histone acetylation and decreasing DNA methylation globally to activate transcription resulted in significant expressional increase of Myosin1C-isoform A in LNCaP cells, but significant expressional decrease in PC3 cells. Taken together, this study shows the cell-specific effects of Androgen receptor, DNA methylation and histone acetylation on the expression of Myosin1C-isoform A. The study, also, provides epigenetic factors as new target to further understand Myosin1C-isoform A gene regulation in PCa and to decrease this isoform expression in invasive PCa cells.