Shi Youwu, Sun Jing, Du Feng, Sun Zhiwei, Yang Ying, Yu Jing, Xiao Yanjie, Sun Xiaoyu, Zhang Wen, Zheng Hongkun, Zhang Xiaodong, Jia Jun
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), the VIP-II Gastrointestinal Cancer Division of Medical Department, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.
Biomarker Technologies Corporation, Beijing, 101300, China.
BMC Gastroenterol. 2025 Jun 5;25(1):433. doi: 10.1186/s12876-025-04048-x.
NDC80, a crucial component of the kinetochore, plays a pivotal role in regulating cell mitosis. Recent studies reported that NDC80 regulates the proliferation of cancer cells and may be related to poor prognosis in cancer. However, the biological function and mechanism of NDC80 in esophageal squamous cell carcinoma (ESCC) have not yet been elucidated. In this study, we analyzed the expression and mutation of NDC80 in ESCC tissue and assessed its impact on ESCC cells in vitro.
A total of 52 ESCC tissues samples were collected and NDC80 gene status was analyzed by whole exome sequence. shRNA was used to knockdown NDC80 expression in two ESCC cell lines TE1 and ECA109 by targeting silence NDC80 gene. Cellular proliferation, apoptosis, migration, and invasion were examined.
Copy number variants (CNVs) of NDC80 were detected in 40.4% (21/52) cancer tissues. Genes with local CNVs values greater than 0.3 were classified as "gain". 23.1% (12/52) of cases showed CNVs gain and 58.3% (7/12) of which with genotype of AAB. Compared with patients of other NDC80 CNVs status, CNVs gain patients had relatively shorter overall survival, however with no statistic difference (19.9 ± 0.8 months vs. 30.9 ± 5.1 months, p = 0.124). Single nucleotide polymorphism mutation of NDC80 was detected in only 5.8% (3/52) cancer tissues including two previous reported mutation rs2271754 and rs6506019, and one novel SNP of C/A-T/G in 2,577,492, GRCh38.p13 intron variant in one case. The knockdown of NDC80 in vitro assays significantly suppressed cellular proliferation and induced increased apoptosis in both TE1 and ECA109 cells. Furthermore, the migration and invasion ability of both TE1 and ECA109 cells were also attenuated upon knockdown of NDC80.
CNVs were identified as the predominant genetic variation of NDC80 gene in ESCC patients. In vitro assays suggested that NDC80 was not only involved into proliferation and apoptosis but also migration and invasion of ESCC cells.
NDC80是动粒的关键组成部分，在调节细胞有丝分裂中起关键作用。最近的研究报道，NDC80调节癌细胞的增殖，可能与癌症预后不良有关。然而，NDC80在食管鳞状细胞癌（ESCC）中的生物学功能和机制尚未阐明。在本研究中，我们分析了NDC80在ESCC组织中的表达和突变情况，并评估了其对ESCC细胞的体外影响。
收集52例ESCC组织样本，通过全外显子测序分析NDC80基因状态。使用shRNA通过靶向沉默NDC80基因来敲低两种ESCC细胞系TE1和ECA109中的NDC80表达。检测细胞增殖、凋亡、迁移和侵袭情况。
在40.4%（21/52）的癌组织中检测到NDC80的拷贝数变异（CNV）。局部CNV值大于0.3的基因被归类为“增益”。23.1%（12/52）的病例显示CNV增益，其中58.3%（7/12）为AAB基因型。与其他NDC80 CNV状态的患者相比，CNV增益患者的总生存期相对较短，但无统计学差异（19.9±0.8个月对30.9±5.1个月，p = 0.124）。仅在5.8%（3/52）的癌组织中检测到NDC80的单核苷酸多态性突变，包括两个先前报道的突变rs2271754和rs6506019，以及一例在2,577,492处的新SNP C/A-T/G，GRCh38.p13内含子变异。体外实验中敲低NDC80可显著抑制TE1和ECA109细胞的增殖并诱导凋亡增加。此外，敲低NDC80后，TE1和ECA109细胞的迁移和侵袭能力也减弱。
CNV被确定为ESCC患者中NDC80基因的主要遗传变异。体外实验表明，NDC80不仅参与ESCC细胞的增殖和凋亡，还参与其迁移和侵袭。
