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Article Open Access

KIAA1429‑mediated ZFPM2‑AS1 m6A modification promotes the proliferation, migration and invasion of osteosarcoma cells

  • Authors:
    • Yuanzhuang Zhang
    • Yuxin Bao
    • Hanjie Zhai
    • Chenghao Li
    • Hongchao Shi
    • Keyang Gong
    • Xiaohe Bao
  • View Affiliations / Copyright

    Affiliations: Fourth Department of Orthopedic Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China, School of Basic Medicine, Shenyang Medical College, Shenyang, Liaoning 110000, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 453
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    Published online on: July 21, 2025
       https://doi.org/10.3892/ol.2025.15199
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Abstract

Osteosarcoma is the most prevalent malignant bone tumor in pediatric and adolescent populations. N6‑methyladenosine (m6A) is a post‑transcriptional modification of RNA, and the most prevalent internal chemical modification of mRNA. KIAA1429, also known as virus‑like m6A methyltransferase‑associated, is a key component of the m6A methyltransferase complex, and the largest protein within this complex. Long non‑coding RNAs (lncRNAs) are a class of transcripts >200 nucleotides in length that are able to regulate gene expression. Friend of GATA family member 2‑antisense 1 (ZFPM2‑AS1) is a lncRNA that has been observed to exhibit aberrantly elevated expression in gastric cancer. The present study aimed to explore the expression levels of KIAA1429 and ZFPM2‑AS1 in osteosarcoma tissues and 143B and MG63 osteosarcoma cell lines. The results of bioinformatics analysis, reverse transcription‑quantitative PCR (qPCR) and western blotting revealed that the expression of KIAA1429 and ZFPM2‑AS1 in osteosarcoma tissues and cell lines was upregulated compared with that in the corresponding normal tissues or cells. The association between KIAA1429‑mediated m6A modifications and ZFPM2‑AS1 stability in osteosarcoma cells was confirmed using m6A‑methylated RNA immunoprecipitation‑qPCR and actinomycin D assays. In addition, in Cell Counting Kit‑8 and Transwell assays KIAA1429 overexpression promoted the proliferation, invasion and migration of 143B and MG63 osteosarcoma cells, and these promotive effects were attenuated by ZFPM2‑AS1 knockdown. These findings suggest a potential novel approach for molecular therapy in the treatment of osteosarcoma.
View Figures

Figure 1

KIAA1429 is upregulated in
osteosarcoma tissues and cell lines. (A) KIAA1429 expression in the
sarcoma dataset from TCGA database, analyzed using UALCAN.
P<0.05 primary tumor vs. normal. (B) KIAA1429 expression in 18
pairs of osteosarcoma tissues and normal tissues from the GSE99671
dataset. *P<0.05 as indicated. (C) Expression of KIAA1429 mRNA
in 20 pairs of osteosarcoma tissues and paraneoplastic tissues
detected by RT-qPCR analysis. ***P<0.001 as indicated. (D)
KIAA1429 protein expression in 5 pairs of osteosarcoma tissues and
paraneoplastic tissues detected by western blotting. **P<0.01 as
indicated. Expression of KIAA1429 in hFOB1.19, 143B and MG63 cells
detected by (E) RT-qPCR analysis and (F) western blotting.
***P<0.001 and ****P<0.0001 vs. hFOB1.19. The data from the
in vitro experiments are presented as the mean ± SD from
three independent experiments. TCGA, The Cancer Genome Atlas;
RT-qPCR, reverse transcription-quantitative PCR.

Figure 2

KIAA1429 knockdown inhibits the
proliferation, migration and invasion of osteosarcoma cells.
Expression levels of KIAA1429 mRNA in (A) 143B and (B) MG63 cells
detected by reverse transcription-quantitative PCR and KIAA1429
protein in (C) 143B and (D) MG63 cells detected by western blotting
following KIAA1429 knockdown. Proliferation of transfected (E) 143B
and (F) MG63 cells detected by Cell Counting Kit-8 assay. Migration
and invasion of transfected (G) 143B and (H) MG63 cells detected by
Transwell assays (scale bar, 200 µm). All data are presented as the
mean ± SD from three independent experiments. *P<0.05,
**P<0.01, ***P<0.001 and ****P<0.0001 vs. shNC.
shKIAA1429, shRNA targeting KIAA1429; shNC, negative control shRNA;
shRNA, short hairpin RNA; OD, optical density.

Figure 3

KIAA1429-mediated m6A
modification is associated with ZFPM2-AS1 stability in osteosarcoma
cells. Correlation of KIAA1429 and ZFPM2-AS1 expression in (A) 87
osteosarcoma tissues from TCGA-TARGET-OS database, (B) 52
osteosarcoma tissues from the GSE87624 osteosarcoma-associated
dataset and (C) 260 sarcoma tissues from TCGA. RT-qPCR detection of
ZFPM2-AS1 expression in (D) 143B and (E) MG63 cells with KIAA1429
knockdown. ****P<0.0001 vs. shNC. (F) ZFPM2-AS1 expression in
sarcoma tissues and normal tissues from TCGA database, analyzed
using UALCAN. P<0.001 primary tumor vs. normal. (G) Kaplan-Meier
analysis of the overall survival of patients with sarcoma based on
ZFPM2-AS1 expression levels. (H) ZFPM2-AS1 expression in 20 pairs
of osteosarcoma and paraneoplastic tissues analyzed by RT-qPCR.
****P<0.0001 as indicated. (I) Expression of ZFPM2-AS1 in
hFOB1.19, 143B and MG63 cells detected by RT-qPCR. ****P<0.0001
vs. hFOB1.19. m6A levels of ZFPM2-AS1 in (J) 5 pairs of
osteosarcoma and paraneoplastic tissues, (K) hFOB1.19, 143B and
MG63 cells, and KIAA1429 knockdown (L) 143B and (M) MG63 cells
determined by MeRIP-qPCR assay. ***P<0.001 and ****P<0.0001
as indicated. Expression levels of ZFPM2-AS1 determined by RT-qPCR
assay in KIAA1429 knockdown (N) 143B and (O) MG63 cells at various
time points after the addition of actinomycin D. ***P<0.001 and
****P<0.0001 as indicated. All data are presented as the mean ±
SD from three independent experiments. m6A,
N6-methyladenosine; ZFPM2-AS1, friend of GATA family
member 2-antisense 1; TCGA, The Cancer Genome Atlas; OS,
osteosarcoma; RT-qPCR, reverse transcription-quantitative PCR;
shNC, negative control shRNA; shKIAA1429, shRNA targeting KIAA1429;
shRNA, short hairpin RNA; FPKM, fragments per kilobase of
transcript per million mapped reads; MeRIP,
m6A-methylated RNA immunoprecipitation.

Figure 4

ZFPM2-AS1 knockdown partially
attenuates the stimulatory effect of KIAA1429 on the proliferation,
migration and invasion of osteosarcoma cells. Western blot analysis
of KIAA1429 protein expression in (A) 143B and (B) MG63 cells
transfected with oeKIAA1429. ****P<0.0001 vs. vector. Expression
of ZFPM2-AS1 in (C) 143B and (D) MG63 cells transfected with
oeKIAA1429 alone or in combination with siZFPM2-AS1 as detected by
reverse transcription-quantitative PCR analysis. Proliferation of
the transfected (E) 143B and (F) MG63 cells detected by Cell
Counting kit-8 assay, and the migration and invasion of the (G)
143B and (H) MG63 cells evaluated using Transwell assays; scale
bar, 200 µm. All data are presented as the mean ± SD from three
independent experiments. ****P<0.0001 vs. vector,
####P<0.0001 vs. oeKIAA1429 + siNC. ZFPM2-AS1, friend
of GATA family member 2-antisense 1; oeKIAA1429, KIAA1429
overexpression; siZFPM2-AS1, siRNA targeting ZFPM2-AS1; siNC,
negative control siRNA; siRNA, small interfering RNA.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang Y, Bao Y, Zhai H, Li C, Shi H, Gong K and Bao X: KIAA1429‑mediated ZFPM2‑AS1 m<sup>6</sup>A modification promotes the proliferation, migration and invasion of osteosarcoma cells. Oncol Lett 30: 453, 2025.
APA
Zhang, Y., Bao, Y., Zhai, H., Li, C., Shi, H., Gong, K., & Bao, X. (2025). KIAA1429‑mediated ZFPM2‑AS1 m<sup>6</sup>A modification promotes the proliferation, migration and invasion of osteosarcoma cells. Oncology Letters, 30, 453. https://doi.org/10.3892/ol.2025.15199
MLA
Zhang, Y., Bao, Y., Zhai, H., Li, C., Shi, H., Gong, K., Bao, X."KIAA1429‑mediated ZFPM2‑AS1 m<sup>6</sup>A modification promotes the proliferation, migration and invasion of osteosarcoma cells". Oncology Letters 30.4 (2025): 453.
Chicago
Zhang, Y., Bao, Y., Zhai, H., Li, C., Shi, H., Gong, K., Bao, X."KIAA1429‑mediated ZFPM2‑AS1 m<sup>6</sup>A modification promotes the proliferation, migration and invasion of osteosarcoma cells". Oncology Letters 30, no. 4 (2025): 453. https://doi.org/10.3892/ol.2025.15199
Copy and paste a formatted citation
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Spandidos Publications style
Zhang Y, Bao Y, Zhai H, Li C, Shi H, Gong K and Bao X: KIAA1429‑mediated ZFPM2‑AS1 m<sup>6</sup>A modification promotes the proliferation, migration and invasion of osteosarcoma cells. Oncol Lett 30: 453, 2025.
APA
Zhang, Y., Bao, Y., Zhai, H., Li, C., Shi, H., Gong, K., & Bao, X. (2025). KIAA1429‑mediated ZFPM2‑AS1 m<sup>6</sup>A modification promotes the proliferation, migration and invasion of osteosarcoma cells. Oncology Letters, 30, 453. https://doi.org/10.3892/ol.2025.15199
MLA
Zhang, Y., Bao, Y., Zhai, H., Li, C., Shi, H., Gong, K., Bao, X."KIAA1429‑mediated ZFPM2‑AS1 m<sup>6</sup>A modification promotes the proliferation, migration and invasion of osteosarcoma cells". Oncology Letters 30.4 (2025): 453.
Chicago
Zhang, Y., Bao, Y., Zhai, H., Li, C., Shi, H., Gong, K., Bao, X."KIAA1429‑mediated ZFPM2‑AS1 m<sup>6</sup>A modification promotes the proliferation, migration and invasion of osteosarcoma cells". Oncology Letters 30, no. 4 (2025): 453. https://doi.org/10.3892/ol.2025.15199
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