Expression of kinetochore component NDC80 promotes esophageal squamous cell carcinoma cells proliferation and migration.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.