The First Department of Oncology, Cangzhou Central Hospital, Cangzhou, Hebei, China.
The First Department of Oncology, Cangzhou Central Hospital, Cangzhou, Hebei, China.
Exp Cell Res. 2018 Jun 15;367(2):216-221. doi: 10.1016/j.yexcr.2018.03.039. Epub 2018 Mar 30.
Colorectal cancer (CRC) is one of the most common cause of cancer-related death in both female and male patients, with a high capacity for tumor migration and invasion. Recently, aberrant nucleolar and spindle-associated protein 1 (NUSAP1) expression has been reported in several cancers. However, the biological function and molecular mechanism of NUSAP1 in CRC have not been reported. Here, we demonstrated that NUSAP1 gene expression was notably upregulated in CRC tissues and cell lines (Caco2, LS174T, SW480, and LoVo). Subsequently, SW480 and LoVo cells were transfected with NUSAP1 siRNA, respectively, and the biological function of NUSAP1 was investigated. Results indicated that NUSAP1 silencing by siRNA inhibited CRC cell proliferation, and induces cell apoptosis. Moreover, NUSAP1 knockdown suppressed cell migration, cell invasion, and epithelial-to-mesenchymal transition (EMT). Furthermore, NUSAP1 silencing notably inhibited the mRNA and protein expression level of DNA methyltransferase 1 (DNMT1). DNMT1 overexpression partly rescued the effect of NUSAP1 silencing on colorectal cancer biological function. Taken together, NUSAP1 gene silencing induced cell apoptosis, and inhibited cell proliferation, cell migration, cell invasion, and EMT in colorectal cancer through inhibiting DNMT1 gene expression. These findings indicat that NUSAP1 is a promising molecular target for CRC treatment.
结直肠癌(CRC)是导致男女患者癌症相关死亡的最常见原因之一,其具有很强的肿瘤迁移和侵袭能力。最近,异常核仁纺锤体相关蛋白 1(NUSAP1)在几种癌症中被报道表达异常。然而,NUSAP1 在 CRC 中的生物学功能和分子机制尚未报道。在这里,我们证明了 NUSAP1 基因表达在 CRC 组织和细胞系(Caco2、LS174T、SW480 和 LoVo)中显著上调。随后,分别用 NUSAP1 siRNA 转染 SW480 和 LoVo 细胞,研究了 NUSAP1 的生物学功能。结果表明,siRNA 沉默 NUSAP1 抑制 CRC 细胞增殖,并诱导细胞凋亡。此外,NUSAP1 敲低抑制细胞迁移、侵袭和上皮间质转化(EMT)。此外,NUSAP1 沉默显著抑制 DNA 甲基转移酶 1(DNMT1)的 mRNA 和蛋白表达水平。DNMT1 的过表达部分挽救了 NUSAP1 沉默对结直肠癌细胞生物学功能的影响。总之,NUSAP1 基因沉默通过抑制 DNMT1 基因表达诱导结直肠癌细胞凋亡,并抑制细胞增殖、迁移、侵袭和 EMT。这些发现表明 NUSAP1 是 CRC 治疗的一个有前途的分子靶点。