Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Department of Gastroenterology, The First People's Hospital of Shunde, Foshan, 528300, China.
Sci Rep. 2017 Jun 16;7(1):3709. doi: 10.1038/s41598-017-04011-1.
RUFY3 is highly expressed in brain tissue and has a role in neuronal development. Transcriptional factor FOXK1 is involved in cell growth and metabolism. We knew that RUFY3 or FOXK1 has been correlated with the malignant of tumor cells. However, the role of these molecules in colorectal cancer (CRC) progression remains unknown. We investigated the protein expression levels by Western blot, immunofluorescence and immunohistochemistry analyses. The migration and invasive abilities of CRC cells were assessed using shRNA-mediated inhibition in vitro and in vivo. We showed that RUFY3 expression was up-regulated in CRC compared with its expression in a normal human colon cell line (FHC). RUFY3 suppression inhibited anchorage independent cell tumorigenesis. RUFY3 induced elevated expression of eight major oncogenes. Moreover, RUFY3 physically interacts with FOXK1 in CRC. A positive correlation was observed between the expression patterns of RUFY3 and FOXK1. Furthermore, RUFY3 and FOXK1 expression were correlated with tumor progression and represented significant predictors of overall survival in CRC patients. SiRNA-mediated repression of FOXK1 in RUFY3-overexpressing cells reversed the epithelial-mesenchymal transition (EMT) and metastatic phenotypes. In vivo, FOXK1 promoted RUFY3-mediated metastasis via orthotopic implantation. These findings suggest that the RUFY3-FOXK1 axis might promote the development and progression of human CRC.
RUFY3 在脑组织中高度表达，在神经元发育中起作用。转录因子 FOXK1 参与细胞生长和代谢。我们知道 RUFY3 或 FOXK1 与肿瘤细胞的恶性有关。然而，这些分子在结直肠癌（CRC）进展中的作用尚不清楚。我们通过 Western blot、免疫荧光和免疫组织化学分析研究了蛋白质表达水平。通过体外和体内 shRNA 介导的抑制来评估 CRC 细胞的迁移和侵袭能力。我们表明，与正常人类结肠细胞系（FHC）相比，CRC 中 RUFY3 的表达上调。RUFY3 抑制抑制了锚定非依赖性细胞肿瘤发生。RUFY3 诱导了八个主要癌基因的高表达。此外，RUFY3 在 CRC 中与 FOXK1 发生物理相互作用。观察到 RUFY3 和 FOXK1 的表达模式之间存在正相关。此外，RUFY3 和 FOXK1 的表达与肿瘤进展相关，并代表 CRC 患者总生存的显著预测因子。在 RUFY3 过表达细胞中，siRNA 介导的 FOXK1 抑制逆转了上皮-间充质转化（EMT）和转移表型。体内，FOXK1 通过原位植入促进了 RUFY3 介导的转移。这些发现表明 RUFY3-FOXK1 轴可能促进人类 CRC 的发展和进展。
