Downregulation of kinetochore‑associated 1 gene increases lagging chromosomes and contributes to chromosomal instability in gastric cancer cells

Gastric cancer (GC) is classified into four molecular subtypes according to the Epstein-Barr virus-positive status, microsatellite instability, genomic stability and chromosomal instability (CIN). The CIN subtype is characterized by a high frequency of gene amplifications in receptor tyrosine kinases (RTKs) and a poor prognosis. In addition, the CIN subtype often exhibits intratumoral heterogeneity and indicates insensitivity to targeted drugs. Elucidating the molecular mechanisms of CIN in GC is therapeutically crucial; however, the molecular mechanisms involved are not yet fully understood. The kinetochore-associated 1 (<i>KNTC1</i>) gene encodes kinetochore-associated protein 1 (KNTC1), a major component of the outer kinetochore. The downregulation of <i>KNTC1</i> causes a high frequency of lagging chromosomes and consequent aneuploidy and CIN in <i>Drosophila</i> and <i>Caenorhabditis elegans</i>. However, the association between <i>KNTC1</i> and CIN in GC has not yet been clarified. Therefore, the present study investigated the role of <i>KNTC1</i> in GC CIN. It was found that GC cell lines with a high frequency of lagging chromosomes had a low <i>KNTC1</i> mRNA expression. Notably, <i>KNTC1</i> knockdown increased the frequency of lagging chromosomes in GC cell lines. In particular, GC cell lines with the amplification of RTK genes exhibited a significant increase in the frequency of lagging chromosomes. On the whole, the findings of the present study suggest that the suppression of <i>KNTC1</i> expression may contribute to CIN in GC and may be involved in the generation of intratumoral genetic heterogeneity in GC.