Ying Cui, Jiang Li, Fei Zheng, Yongri Ouyang, Xi Chen, Lei Zhang, Yang Chen, Lin Wang, Shijie Mu, Huizhong Zhang
Department of Blood Transfusion, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shanxi, China (mainland)
Med Sci Monit 2016; 22:380-386
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