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Article Open Access

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

  • Authors:
    • Daiki Ohsaki
    • Kazuki Kanayama
  • View Affiliations / Copyright

    Affiliations: Graduate School of Health Science, Suzuka University of Medical Science, Suzuka, Mie 510‑0293, Japan
    Copyright: © Ohsaki et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 59
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    Published online on: August 4, 2025
       https://doi.org/10.3892/mi.2025.258
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Abstract

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 (KNTC1) gene encodes kinetochore‑associated protein 1 (KNTC1), a major component of the outer kinetochore. The downregulation of KNTC1 causes a high frequency of lagging chromosomes and consequent aneuploidy and CIN in Drosophila and Caenorhabditis elegans. However, the association between KNTC1 and CIN in GC has not yet been clarified. Therefore, the present study investigated the role of KNTC1 in GC CIN. It was found that GC cell lines with a high frequency of lagging chromosomes had a low KNTC1 mRNA expression. Notably, KNTC1 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 KNTC1 expression may contribute to CIN in GC and may be involved in the generation of intratumoral genetic heterogeneity in GC.
View Figures

Figure 1

Representative image of lagging
chromosomes in NCI-N87 cells. Chromosomes remained on the metaphase
plate and formed bridges in anaphase (red arrow).

Figure 2

Frequency of lagging chromosomes in
the NCI-N87, KATOIII, MKN74 and TIG-1-20 cells. The frequency of
lagging chromosomes was significantly higher in the NCI-N87 and
KATOIII cells than in the MKN74 cells. All data were analyzed using
one-way ANOVA and Tukey-Kramer test. **P#x003C;0.01.

Figure 3

mRNA expression levels of KNTC1
in the NCI-N87, KATOIII, MKN74 and TIG-1-20 cells, as measured
using reverse transcription-quantitative PCR. KNTC1 mRNA
expression was higher in the MKN74 cells than in the NCI-N87 and
KATOIII cells and was inversely associated with the frequency of
lagging chromosomes. All data were analyzed using one-way ANOVA and
Tukey-Kramer test. *P#x003C;0.05. KNTC1,
kinetochore-associated 1 gene.

Figure 4

The NCI-N87, KATOIII, MKN74 and
TIG-1-20 cells were transfected with siRNA targeting KNTC1
or negative control (siControl). At 3 days following transfection,
total RNA was extracted and measured using reverse
transcription-quantitative PCR. KNTC1 mRNA expression was
significantly decreased following transfection with siRNA targeting
KNTC1 in all cell lines. All data were analyzed using the
Student's t-test. **P#x003C;0.01 vs. siControl
KNTC1, kinetochore-associated 1 gene.

Figure 5

Frequencies of lagging chromosomes in
NCI-N87, MKN74, TIG-1-20 and KATOIII cells transfected with siRNA
targeting KNTC1 or negative control (siControl) for 3 days.
(A) The frequency of lagging chromosomes was significantly
increased in the NCI-N87 and KATOIII cells transfected with siRNA
targeting KNTC1. All data were analyzed using the Student's t-test.
*P#x003C;0.05 vs. siControl; **P#x003C;0.01
vs. siControl. (B) The silencing off KNTC1 could lead to
intratumoral genetic heterogeneity in GC cells with the
amplification of RTK genes. KNTC1, kinetochore-associated 1
gene; GC, gastric cancer; RTKs, receptor tyrosine kinases.

Figure 6

ZW10 expression in NCI-N87, KATOIII,
MKN74 and TIG-1-20 cells. Cells were transfected with siRNA
targeting KNTC1 or negative control (siControl). (A) ZW10
expression was evaluated using western blot analysis, with
α-tubulin as the loading control. (B) Quantitative analysis using
ImageLab software. No change in ZW10 expression was observed
following the knockdown of KNTC1. All data were analyzed
using the Student's t-test. KNTC1, kinetochore-associated 1
gene.
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Spandidos Publications style
Ohsaki D and Kanayama K: Downregulation of kinetochore‑associated 1 gene increases lagging chromosomes and contributes to chromosomal instability in gastric cancer cells. Med Int 5: 59, 2025.
APA
Ohsaki, D., & Kanayama, K. (2025). Downregulation of kinetochore‑associated 1 gene increases lagging chromosomes and contributes to chromosomal instability in gastric cancer cells. Medicine International, 5, 59. https://doi.org/10.3892/mi.2025.258
MLA
Ohsaki, D., Kanayama, K."Downregulation of kinetochore‑associated 1 gene increases lagging chromosomes and contributes to chromosomal instability in gastric cancer cells". Medicine International 5.5 (2025): 59.
Chicago
Ohsaki, D., Kanayama, K."Downregulation of kinetochore‑associated 1 gene increases lagging chromosomes and contributes to chromosomal instability in gastric cancer cells". Medicine International 5, no. 5 (2025): 59. https://doi.org/10.3892/mi.2025.258
Copy and paste a formatted citation
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Spandidos Publications style
Ohsaki D and Kanayama K: Downregulation of kinetochore‑associated 1 gene increases lagging chromosomes and contributes to chromosomal instability in gastric cancer cells. Med Int 5: 59, 2025.
APA
Ohsaki, D., & Kanayama, K. (2025). Downregulation of kinetochore‑associated 1 gene increases lagging chromosomes and contributes to chromosomal instability in gastric cancer cells. Medicine International, 5, 59. https://doi.org/10.3892/mi.2025.258
MLA
Ohsaki, D., Kanayama, K."Downregulation of kinetochore‑associated 1 gene increases lagging chromosomes and contributes to chromosomal instability in gastric cancer cells". Medicine International 5.5 (2025): 59.
Chicago
Ohsaki, D., Kanayama, K."Downregulation of kinetochore‑associated 1 gene increases lagging chromosomes and contributes to chromosomal instability in gastric cancer cells". Medicine International 5, no. 5 (2025): 59. https://doi.org/10.3892/mi.2025.258
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