Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Department of Gastroenterology, Hexian Memorial Affiliated Hospital of Southern Medical University, Guangzhou, 511400, China.
Cancer Lett. 2017 Apr 1;390:30-38. doi: 10.1016/j.canlet.2017.01.001. Epub 2017 Jan 13.
Rufy3 is a RUN domain-containing protein that has been associated with gastric cancers; however, the role of Rufy3 in the progression of colorectal cancer (CRC) remains unknown. We demonstrated that Rufy3 expression was higher in 11/12 fresh CRC tissues than in adjacent normal tissues. Rufy3 induced elevated expression and transactivity of four major oncogenes in CRC. Moreover, siRNA-mediated repression of Rufy3 induced G0/G1 cell cycle arrest, and Rufy3 overexpression enhanced CRC cell proliferation in vitro and in vivo. Furthermore, Rufy3 up-regulation promoted epithelial-mesenchymal transition (EMT) and metastatic phenotypes. Using an established in vitro cell model of 5-fluorouracil-resistant (5-FU) CRC cells, we assessed cellular morphology, molecular changes, and invasion and found that these characteristics were consistent with EMT. Silencing of Rufy3 by siRNA reversed EMT and greatly diminished the invasion of 5-FU-treated cells. In addition, TGF-β1 induced Rufy3 expression in a dose-dependent manner, and Rufy3 knockdown inhibited TGF-β1-induced EMT. In vivo, higher expression of Rufy3 promoted CRC cell invasion and metastasis and induced EMT. Taken together, this work identified that Rufy3 promoted cancer metastasis in CRC cells through EMT induction.
Rufy3 是一种含有 RUN 结构域的蛋白，与胃癌相关；然而，Rufy3 在结直肠癌（CRC）进展中的作用尚不清楚。我们证明，在 11/12 例新鲜 CRC 组织中 Rufy3 的表达高于相邻正常组织。Rufy3 诱导 CRC 中四个主要癌基因的高表达和转录活性。此外，siRNA 介导的 Rufy3 抑制诱导 G0/G1 细胞周期停滞，而过表达 Rufy3 增强 CRC 细胞在体外和体内的增殖。此外，Rufy3 的上调促进了上皮-间充质转化（EMT）和转移表型。使用建立的氟尿嘧啶耐药（5-FU）CRC 细胞体外细胞模型，我们评估了细胞形态、分子变化和侵袭，发现这些特征与 EMT 一致。siRNA 沉默 Rufy3 逆转了 EMT，并大大减少了 5-FU 处理细胞的侵袭。此外，TGF-β1 以剂量依赖的方式诱导 Rufy3 的表达，而 Rufy3 的敲低抑制了 TGF-β1 诱导的 EMT。在体内，Rufy3 的高表达促进了 CRC 细胞的侵袭和转移，并诱导了 EMT。总之，这项工作表明 Rufy3 通过 EMT 诱导促进了 CRC 细胞的癌症转移。
