Lentivirus-mediated RNA interference targeting WWTR1 in human colorectal cancer cells inhibits cell proliferation in vitro and tumor growth in vivo

摘要

WW domain-containing transcription regulator 1 (WWTR1) was initially identified as a transcriptional coactivator involved in the differentiation of stem cells as well as the development of multiple organs. Recently, WWTR1 has also been identified as a major component of the novel Hippo signalling pathway important for the development of breast and lung cancer. Here, we show for the first time that WWTR1 has an oncogenic function in colorectal cancer cell lines. Knockdown of WWTR1 by lentivirus-mediated RNA interference in human colorectal cancer cells significantly decreased cell proliferation and the colony formation of RKO cells in vitro and tumor growth in vivo. Furthermore, we found that the decreased proliferation was due to cell cycle arrest and increased apoptosis. In addition, efficient knockdown of WWTR1, demonstrated by quantitative real-time PCR, led to upregulation of ASNS and downregulation of SMAD3, LTBR, BAX and BAK1 in WWTR1 knockdown cells, suggesting that these genes may be involved in the repression of cell proliferation. Our findings indicate that WWTR1 is an oncogene and has an important role in the proliferation of colorectal cancer cells and in tumor growth in vivo.