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Histone acetyltransferase 1 promotes ovarian cancer progression by regulating cell proliferation and the cell cycle

  • Authors:
    • Xiao Han
    • Ling Liu
    • Jing Li
    • Yunxiao Zhi
    • Lanlan Zhao
    • Limin Yuan
    • Xuezhe Ouyang
    • Jie Liu
  • View Affiliations / Copyright

    Affiliations: Department of Medical Genetic and Prenatal Diagnosis, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou University, Zhengzhou, Henan 450008, P.R. China
    Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 539
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    Published online on: September 22, 2025
       https://doi.org/10.3892/ol.2025.15285
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Abstract

Ovarian cancer (OC) is the most common cause of gynecological cancer‑related death. Histone acetyltransferase 1 (HAT1) has generated interest as a potential target for therapy due to it being involved in a variety of diseases, including cancer. However, to the best of our knowledge, the role of HAT1 in OC has not yet been investigated. In the present study, HAT1 was upregulated in OC and the high expression of HAT1 was associated with unfavorable prognosis. The transcription factor forkhead box protein A1 (FOXA1) transcriptionally regulated HAT1 expression. Furthermore, HAT1 knockdown in OC cells significantly suppressed cell proliferation and colony formation. In addition, the inhibition of HAT1 promoted cell cycle arrest, and reduced cyclin‑dependent kinase (CDK)2, CDK4 and cyclin E levels in OC cells. Taken together, the present data suggested that HAT1 served an oncogenic role in OC; therefore, HAT1 may represents a new potential therapeutic target in OC treatment.
View Figures

Figure 1

HAT1 levels are upregulated in human
ovarian cancer tissue and higher HAT1 levels indicate a poor
prognosis. (A) Representative images depicting the representative
immunostaining of HAT1 in ovarian cancer tissues and healthy human
tissues in The Human Protein Altas database. Scale bar=200 µm. (B)
Analysis of the TNMplot database showed that HAT1 was highly
expressed in ovarian cancer tissues compared with healthy controls.
(C) Protein levels of HAT1 in ovarian cancer and healthy human
samples from healthy controls were analyzed in the CPTAC database.
(D) HAT1 protein levels were upregulated with tumor grade in
ovarian cancer tissues. (E) Higher HAT1 levels were associated with
an unfavorable prognosis in patients with ovarian cancer. Data are
presented as the mean ± SD. **P<0.01. HAT1, histone
acetyltransferase 1; CPTAC, Clinical Proteomic Tumor Analysis
Consortium; HR, hazard ratio.

Figure 2

HAT1 expression levels are
upregulated in human ovarian cancer cell lines. (A) Relative
expression levels of HAT1 were detected by reverse
transcription-quantitative PCR in A2780, HEY, OVCAR3, SKOV3 and
normal IOSE386 cell lines. (B) Western blot analysis of HAT1
expression in A2780, HEY, OVCAR3, SKOV3 and IOSE386 cell lines.
****P<0.0001 vs. IOSE386. HAT1, histone acetyltransferase 1.

Figure 3

FOXA1 transcriptionally regulates
HAT1 expression levels. (A) FOXA1 binding sites in the HAT1
promoter region were predicted using the JASPAR database. MUT
constructs were generated at the binding sequence regions as
indicated. (B) The expression levels of FOXA1 in HEY cells
transfected with an empty or FOXA1 vector. (C) HEY cells were
transfected with pmirGLO reporter vectors containing either WT or
MUT plasmids alongside an empty or FOXA1 vector. Luciferase
activities were determined 24 h after transfection. (D)
Overexpression of FOXA1 induced HAT1 expression levels. (E)
cBioPortal database was adopted to analyze the correlation between
FOXA1 and HAT1. Pearson's rank correlation between HAT1 and FOXA1
was analyzed in ovarian cancer tissues. (F) FOXA1 levels in ovarian
cancer tissues from TCGA were determined using TNMplot database.
(G) FOXA1 was enriched at the HAT1 promoter region as suggested by
Cistrome DB. Data are presented as the mean ± SD of three
replicates. **P<0.01 vs. vector or as indicated; ns, not
significant. ChIP-seq, chromatin immunoprecipitation sequencing;
FOXA1, forkhead box protein A1; HAT1, histone acetyltransferase 1;
WT, wild-type; MUT, mutant.

Figure 4

Relationship between HAT1 and DNA
replication and pyrimidine metabolism pathways. (A) LinkedOmics
database suggested that differentially expressed genes of HAT1 were
enriched in several biological processes, such as ‘DNA
replication’, ‘pyrimidine metabolism’ and ‘RNA transport’. (B) Gene
set enrichment analysis revealed that genes altered by HAT1 were
positively associated with ‘DNA replication’ as well as ‘pyrimidine
metabolism’ pathways. (C) cBioPortal database was used to analyze
the correlations between HAT1 and regulatory proteins of the DNA
replication pathway. Pearson's rank correlation between HAT1 and
DNA replication-related proteins (PCNA, RPA1 and POLA1) was
analyzed in ovarian cancer tissues. (D) Pearson's rank correlation
between HAT1 and pyrimidine metabolism-related proteins (TK1, RRM1
and RRM2) was analyzed in ovarian cancer tissues as suggested in
the cBioPortal database. HAT1, histone acetyltransferase 1; PCNA,
proliferating cell nuclear antigen; RPA1, replication protein A1;
POLA1, DNA polymerase α catalytic subunit; TK1, thymidine kinase 1;
RRM, ribonucleoside-diphosphate reductase subunit M; NES,
normalized enrichment score; FDR, false discovery rate.

Figure 5

Inhibition of HAT1 suppresses cell
viability and colony formation in vitro. (A) Western blot
analysis of HAT1 expression in HEY and SKOV3 cells transfected with
HAT1 siRNA or NC siRNA. (B) Cell Counting Kit-8 assays were
performed to determine cell viability after HAT1 was knocked down
in HEY and SKOV3 cells. (C) HEY and SKOV3 cells were treated with
HAT1 inhibitor JG-2016 for 72 h, which significantly inhibited cell
viability. (D) Knockdown of HAT1 decreased the colony formation
capacity of HEY and SKOV3 cells. Data are presented as the mean ±
SD of three replicates. *P<0.05 and **P<0.01 vs. siNC in
figure 5B and DMSO group in figure 5C. HAT1, histone
acetyltransferase 1; si, small interfering; NC, negative
control.

Figure 6

HAT1 knockdown inhibits cell
proliferation. (A) EdU assays of HEY cells were performed showing
that suppression of HAT1 attenuated cell proliferation activities.
Scale bar, 20 µm. (B) Cell cycle analysis was carried out on the
HAT1 knockdown and siNC cell lines, and the distribution of
G0/G1, S and G2/M percentages were
analyzed. (C) Western blot analysis of cell cycle-related protein
expression after knockdown of HAT1. (D) Pearson's rank correlation
between HAT1 and CDK2, CDK4 and cyclin E was analyzed in ovarian
cancer tissues. Data are presented as the mean ± SD of three
replicates. **P<0.01 vs. siNC. HAT1, histone acetyltransferase
1; si, small interfering; NC, negative control; CDK,
cyclin-dependent kinase.
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Copy and paste a formatted citation
Spandidos Publications style
Han X, Liu L, Li J, Zhi Y, Zhao L, Yuan L, Ouyang X and Liu J: Histone acetyltransferase 1 promotes ovarian cancer progression by regulating cell proliferation and the cell cycle. Oncol Lett 30: 539, 2025.
APA
Han, X., Liu, L., Li, J., Zhi, Y., Zhao, L., Yuan, L. ... Liu, J. (2025). Histone acetyltransferase 1 promotes ovarian cancer progression by regulating cell proliferation and the cell cycle. Oncology Letters, 30, 539. https://doi.org/10.3892/ol.2025.15285
MLA
Han, X., Liu, L., Li, J., Zhi, Y., Zhao, L., Yuan, L., Ouyang, X., Liu, J."Histone acetyltransferase 1 promotes ovarian cancer progression by regulating cell proliferation and the cell cycle". Oncology Letters 30.6 (2025): 539.
Chicago
Han, X., Liu, L., Li, J., Zhi, Y., Zhao, L., Yuan, L., Ouyang, X., Liu, J."Histone acetyltransferase 1 promotes ovarian cancer progression by regulating cell proliferation and the cell cycle". Oncology Letters 30, no. 6 (2025): 539. https://doi.org/10.3892/ol.2025.15285
Copy and paste a formatted citation
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Spandidos Publications style
Han X, Liu L, Li J, Zhi Y, Zhao L, Yuan L, Ouyang X and Liu J: Histone acetyltransferase 1 promotes ovarian cancer progression by regulating cell proliferation and the cell cycle. Oncol Lett 30: 539, 2025.
APA
Han, X., Liu, L., Li, J., Zhi, Y., Zhao, L., Yuan, L. ... Liu, J. (2025). Histone acetyltransferase 1 promotes ovarian cancer progression by regulating cell proliferation and the cell cycle. Oncology Letters, 30, 539. https://doi.org/10.3892/ol.2025.15285
MLA
Han, X., Liu, L., Li, J., Zhi, Y., Zhao, L., Yuan, L., Ouyang, X., Liu, J."Histone acetyltransferase 1 promotes ovarian cancer progression by regulating cell proliferation and the cell cycle". Oncology Letters 30.6 (2025): 539.
Chicago
Han, X., Liu, L., Li, J., Zhi, Y., Zhao, L., Yuan, L., Ouyang, X., Liu, J."Histone acetyltransferase 1 promotes ovarian cancer progression by regulating cell proliferation and the cell cycle". Oncology Letters 30, no. 6 (2025): 539. https://doi.org/10.3892/ol.2025.15285
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