Mu Yu, Zou Hongzhi, Chen Beibei, Fan Yixiao, Luo Suxia
Department of Medical Oncology, the Tumor Hospital of Zhengzhou University, Henan Tumor Hospital, Zhengzhou University, Zhengzhou 450008, Henan, China.
Department of Medical Oncology, the Tumor Hospital of Zhengzhou University, Henan Tumor Hospital, Zhengzhou University, Zhengzhou 450008, Henan, China.
Biomed Pharmacother. 2017 Jun;90:548-554. doi: 10.1016/j.biopha.2017.03.073. Epub 2017 Apr 11.
Colorectal cancer is one of the most common malignant tumors in the digestive system, and in China its incidence is rising in recent years. The FAM83D family with sequence similarity 83, member D is associated with the occurrence and development of various cancers. However, in human colorectal cancer, the biological function of FAM83D and its molecular mechanism are still little known. In our study, we found that FAM83D mRNA expression level was markedly up-regulated in colorectal cancerous tissues when compared with that of adjacent normal colon tissues. We also found that the protein and mRNA expression levels of FAM83D are dramatically increased in human colorectal cancer cell lines, including Caco-2, RKO, DLD-1, HT-29, LoVo, SW480, and HCT116, especially in SW480 and HCT116 cells, when compared with that of human normal colon epithelial cell line (NCM460). Next, in HCT116 and SW480 cells, the biological function of FAM83D was examined. FAM83D-knockdown notably inhibited cell proliferation and colony formation. Cell apoptosis was promoted by FAM83D knockdown. In addition, FAM83D siRNA decreased cell migration and invasion. Moreover, FAM83D knockdown up-regulated the protein expression level of F-box and WD repeat domain-containing 7 (FBXW7), but diminished the Notch1 protein expression level. It also found that FBXW7 siRNA reverses the suppressive effect of FAM83D knockdown on Notch1 protein expression. Notch1 overexpression reversed the effect of FAM83D knockdown on colorectal cancer cell proliferation, cell migration and invasion. In conclusion, FAM83D knockdown promoted colorectal cancer cell apoptosis, inhibited cell proliferation, cell migration and invasion, which might be associated with inhibiting the FBXW7/Notch1 signal pathway. Our findings indicated that FAM83D is a promising molecular target for colorectal cancer treatment.
结直肠癌是消化系统最常见的恶性肿瘤之一，近年来在中国其发病率呈上升趋势。序列相似性83成员D（FAM83D）家族与多种癌症的发生和发展相关。然而，在人类结直肠癌中，FAM83D的生物学功能及其分子机制仍鲜为人知。在我们的研究中，我们发现与相邻正常结肠组织相比，FAM83D mRNA在结直肠癌组织中的表达水平显著上调。我们还发现，与人类正常结肠上皮细胞系（NCM460）相比，FAM83D的蛋白质和mRNA表达水平在包括Caco-2、RKO、DLD-1、HT-29、LoVo、SW480和HCT116在内的人类结直肠癌细胞系中显著增加，尤其是在SW480和HCT116细胞中。接下来，在HCT116和SW480细胞中检测了FAM83D的生物学功能。FAM83D敲低显著抑制细胞增殖和集落形成。FAM83D敲低促进细胞凋亡。此外，FAM83D siRNA降低细胞迁移和侵袭。而且，FAM83D敲低上调含F盒和WD重复结构域7（FBXW7）的蛋白质表达水平，但降低Notch1蛋白质表达水平。还发现FBXW7 siRNA可逆转FAM83D敲低对Notch1蛋白质表达的抑制作用。Notch1过表达逆转了FAM83D敲低对结直肠癌细胞增殖、细胞迁移和侵袭的影响。总之，FAM83D敲低促进结直肠癌细胞凋亡，抑制细胞增殖、细胞迁移和侵袭，这可能与抑制FBXW7/Notch1信号通路有关。我们的研究结果表明，FAM83D是结直肠癌治疗的一个有前景的分子靶点。
