Effect of SIRT1 Gene on Epithelial-Mesenchymal Transition of Human Prostate Cancer PC-3 Cells

BACKGROUND: The epithelial-mesenchymal transition (EMT) has been shown to be involved in the process of invasion and metastasis of prostate cancer. SIRT1 is the mammalian homologue of the silent information regulator 2 (Sir2) gene, and is abnormally expressed in prostate cancer cells. Therefore, it is hypothesized that SIRT1 mediates the invasion/metastatic ability of prostate cancer via EMT regulation. This study thus investigated the effect of SIRT1 gene on the invasion and migration of prostate cancer cell line PC-3 via the small interference RNA (siRNA) against SIRT1.
MATERIAL AND METHODS: SiRNA construct was transfected into PC-3 cells, which were tested for the cell migration and invasion ability by scratch assay and Transwell migration assay, respectively. Expression levels of vimentin, E-cadherin, and N-cadherin were further quantified by Western blotting and RT-PCR.
RESULTS: Both mRNA and protein levels of SIRT1 were depressed after siRNA transfection, along with weakened migration and invasion ability of PC-3 cells. Elevated E-cadherin and suppressed N-cadherin and vimentin were observed in those transfected cells.
CONCLUSIONS: The silencing of SIRT1 gene in PC-3 cells can suppress the movement, migration, and invasion functions of prostate cancer cells, possibly via the down-regulation of mesenchymal markers vimentin and N-cadherin accompanied with up-regulation of epithelial marker N-cadherin, thus reversing the EMT process.

Keywords: Cell Line, Tumor, Cadherins - metabolism, Cell Movement - genetics, Cellulose 1,4-beta-Cellobiosidase - metabolism, Down-Regulation, Epithelial-Mesenchymal Transition - genetics, Prostatic Neoplasms - pathology, RNA, Small Interfering, Sirtuin 1 - metabolism, Transfection, Up-Regulation, Vimentin - metabolism