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KIAA1429 knockdown alleviates osteosarcoma  progression by destabilizing SLC7A11 mRNA via m6A methylation to promote ferroptosis

  • Authors:
    • Hui Zeng
    • Yunyan Zhong
    • Dingbiao Zeng
    • Shiliang Xiao
    • Song Zou
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, Ganzhou People's Hospital, Ganzhou, Jiangxi 341000, P.R. China, Department of Medical Records, Ganzhou People's Hospital, Ganzhou, Jiangxi 341000, P.R. China, Department of Interventional Radiology and Vascular Surgery, Ganzhou Key Laboratory of Interventional Medicine, Ganzhou Hospital-Nanfang Hospital, Southern Medical University (Ganzhou People's Hospital), Ganzhou, Jiangxi 341000, P.R. China
    Copyright: © Zeng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 116
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    Published online on: August 17, 2026
       https://doi.org/10.3892/ijo.2026.5929
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Abstract

Osteosarcoma (OS) is a highly aggressive bone tumor with limited therapeutic options. As a key component of the N6‑methyladenosine (m6A) methyltransferase complex, KIAA1429 contributes to tumor progression; however, its role in OS remains unclear. For the present study, four human OS cell lines (MG63, 143B, U2OS and Saos‑2) and an osteoblast cell line (hFOB1.19) were cultured in vitro, and KIAA1429 was knocked down in 143B and U2OS cells. To evaluate functional effects, cell proliferation was assessed using a Cell Counting Kit‑8 assay, apoptosis was evaluated by flow cytometry, migration was assessed by Transwell assay and invasion was analyzed using a wound healing assay. Subsequently, ferroptosis was induced using erastin, and analyzed by western blotting, ELISA, C11‑BODIPY staining and m6A‑modified RNA immunoprecipitation‑quantitative PCR. In addition, actinomycin D was used to inhibit transcription and to assess mRNA stability. The interaction between KIAA1429 and solute carrier family 7 member 11 (SLC7A11) was validated using a dual‑luciferase reporter assay. Furthermore, a xenograft model was established in BALB/c nude mice to assess tumor growth and ferroptosis markers, and tumor histology and proliferation were examined using hematoxylin and eosin staining and immunohistochemistry. The results revealed that KIAA1429 was significantly upregulated in OS cells, whereas its knockdown markedly suppressed malignant cellular behaviors. Downregulation of KIAA1429 also enhanced erastin‑induced ferroptosis. Mechanistically, KIAA1429 knockdown reduced m6A modification and decreased the stability of SLC7A11 mRNA, leading to its downregulation. Rescue experiments demonstrated that SLC7A11 overexpression reversed the effects of KIAA1429 knockdown on ferroptosis and malignant phenotypes. In vivo, KIAA1429 knockdown inhibited tumor growth and promoted ferroptosis, effects that were reversed by SLC7A11 overexpression. In conclusion, KIAA1429 knockdown may suppress OS progression by inhibiting m6A‑dependent SLC7A11 expression, thereby promoting ferroptosis. Targeting the KIAA1429/SLC7A11 axis may thus represent a promising therapeutic strategy for OS.
View Figures

Figure 1

KIAA1429 knockdown suppresses OS cell
proliferation and promotes apoptosis. (A) KIAA1429 expression in OS
cell lines was detected by western blotting. **P<0.01
vs. hFOB 1.19 group. (B) KIAA1429 knockdown efficiency was measured
by western blotting. (C) Cell proliferation was assessed by Cell
Counting Kit-8 assay. (D) Apoptosis detection via flow cytometry.
**P<0.01 vs. si-NC group. NC, negative control; OD,
optical density; OS, osteosarcoma; PI, propidium iodide; si, small
interfering.

Figure 2

KIAA1429 knockdown suppresses
osteosarcoma cell invasion and migration. (A) Cell invasion was
measured by Transwell assay (magnification, ×200; scale bar, 100
μm). (B) Cell migration was evaluated by wound healing assay
(magnification, ×200; scale bar, 100 μm).
**P<0.01 vs. si-NC group. NC, negative control; si,
small interfering.

Figure 3

KIAA1429 knockdown promotes
ferroptosis in osteosarcoma cells. (A) Cell viability was evaluated
by Cell Counting Kit-8 assay. (B) Protein expression levels of
ferroptosis-related markers were measured by western blotting. (C)
ELISA was performed to evaluate levels of MDA, Fe2+, GSH
and ROS. (D) C11-BODIPY staining for lipid peroxidation
(magnification, ×200; scale bar, 100 μm).
*P<0.05, **P<0.01 vs. si-NC;
#P<0.05, ##P<0.01 vs. si-NC group.
COX2, cytochrome c oxidase 2; GPX4, GSH peroxidase 4; GSH,
glutathione; MDA, malondialdehyde; NC, negative control; ROS,
reactive oxygen species; si, small interfering.

Figure 4

Mechanistic regulation of SLC7A11 by
KIAA1429 through m6A modification. (A) SLC7A11 expression in
osteosarcoma cell lines was detected by western blotting.
**P<0.01 vs. hFOB1.19. (B) mRNA and (C) protein
levels of SLC7A11 in transfected 143B and U2OS cells were measured
by reverse transcription-qPCR and western blotting, respectively.
(D) m6A enrichment of SLC7A11 was measured by m6A-modified RNA
immunoprecipitation-qPCR. (E) Stability of SLC7A11 after
actinomycin treatment was detected by qPCR. (F) Dual luciferase
assay was used to verify the interaction between KIAA1429 and
SLC7A11. **P<0.01 vs. si-NC. m6A, N6-methyladenosine;
MUT, mutant; NC, negative control; qPCR, quantitative PCR; si,
small interfering; SLC7A11, solute carrier family 7 member 11; WT,
wild-type.

Figure 5

KIAA1429 knockdown suppresses
viability and promotes apoptosis in OS cells via SLC7A11. (A)
Reverse transcription-quantitative PCR was performed to detect the
mRNA levels of SLC7A11 in OS cell lines. **P<0.01 vs.
oe-NC. (B) Cell viability was measured by Cell Counting Kit-8
assay. (C) Apoptosis was evaluated by flow cytometry.
**P<0.01 vs. si-NC; ##P<0.01 vs.
si-KIAA1429. NC, negative control; OD, optical density; oe,
overexpression vector; OS, osteosarcoma; si, small interfering;
SLC7A11, solute carrier family 7 member 11.

Figure 6

KIAA1429 knockdown suppresses
invasion, migration and epithelial-mesenchymal transition in OS
cells via SLC7A11. (A) Invasive potential was measured by Transwell
assay (magnification, ×200; scale bar, 100 μm). (B)
Migratory capacity was evaluated by wound healing assay
(magnification, ×200; scale bar, 100 μm). (C) Western blot
analysis of E-cadherin and Vimentin expression.
**P<0.01 vs. si-NC; ##P<0.01 vs.
si-KIAA1429. NC, negative control; OD, optical density; oe,
overexpression vector; OS, osteosarcoma; si, small interfering;
SLC7A11, solute carrier family 7 member 11.

Figure 7

KIAA1429/SLC7A11 axis regulates
ferroptosis in osteosarcoma. (A) Cell viability was assessed by
Cell Counting Kit-8 assay. (B) Levels of oxidative stress
parameters (Fe2+, MDA, GSH, and ROS) were assessed by
ELISA. (C) Ferroptosis markers (COX2 and GPX4) were measured by
western blotting. (D) Western blot analysis of E-cadherin and
Vimentin expression. **P<0.01 vs. si-NC;
##P<0.01 vs. si-NC + erastin;
&P<0.05, &&P<0.01 vs.
si-KIAA1429 + erastin. COX2, cytochrome c oxidase 2; GPX4,
GSH peroxidase 4; GSH, glutathione; MDA, malondialdehyde; NC,
negative control; oe, overexpression vector; ROS, reactive oxygen
species; si, small interfering; SLC7A11, solute carrier family 7
member 11.

Figure 8

KIAA1429 knockdown suppresses
osteosarcoma growth and ferroptosis in vivo. (A) Reverse
transcription-quantitative PCR was performed to detect the mRNA
levels of KIAA1429 in tumor tissues. (B) Subcutaneous tumor
formation. (C) Tumor volume and weight quantification. (D)
Histopathological analysis was observed by H&E staining
(magnification, ×400; scale bar, 20 μm). Arrows indicate
inflammatory infiltration. (E) Proliferation marker Ki67 was
observed by IHC (magnification, ×400; scale bar, 20 μm). (F)
Levels of oxidative stress parameters (MDA, GSH, Fe2+
and ROS) were evaluated by ELISA. (G) Protein expression levels of
ferroptosis biomarkers were assessed by western blotting.
**P<0.01 vs. lv-sh-NC; #P<0.05,
##P<0.01 vs. lv-sh-KIAA1429. COX2, cytochrome
c oxidase 2; GPX4, GSH peroxidase 4; GSH, glutathione;
H&E, hematoxylin and eosin; IHC, immunohistochemistry; lv,
lentivirus; MDA, malondialdehyde; NC, negative control; ns, not
significant; ROS, reactive oxygen species; sh, short hairpin;
SLC7A11, solute carrier family 7 member 11.
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Copy and paste a formatted citation
Spandidos Publications style
Zeng H, Zhong Y, Zeng D, Xiao S and Zou S: KIAA1429 knockdown alleviates osteosarcoma&nbsp; progression by destabilizing SLC7A11 mRNA via m6A methylation to promote ferroptosis. Int J Oncol 69: 116, 2026.
APA
Zeng, H., Zhong, Y., Zeng, D., Xiao, S., & Zou, S. (2026). KIAA1429 knockdown alleviates osteosarcoma&nbsp; progression by destabilizing SLC7A11 mRNA via m6A methylation to promote ferroptosis. International Journal of Oncology, 69, 116. https://doi.org/10.3892/ijo.2026.5929
MLA
Zeng, H., Zhong, Y., Zeng, D., Xiao, S., Zou, S."KIAA1429 knockdown alleviates osteosarcoma&nbsp; progression by destabilizing SLC7A11 mRNA via m6A methylation to promote ferroptosis". International Journal of Oncology 69.4 (2026): 116.
Chicago
Zeng, H., Zhong, Y., Zeng, D., Xiao, S., Zou, S."KIAA1429 knockdown alleviates osteosarcoma&nbsp; progression by destabilizing SLC7A11 mRNA via m6A methylation to promote ferroptosis". International Journal of Oncology 69, no. 4 (2026): 116. https://doi.org/10.3892/ijo.2026.5929
Copy and paste a formatted citation
x
Spandidos Publications style
Zeng H, Zhong Y, Zeng D, Xiao S and Zou S: KIAA1429 knockdown alleviates osteosarcoma&nbsp; progression by destabilizing SLC7A11 mRNA via m6A methylation to promote ferroptosis. Int J Oncol 69: 116, 2026.
APA
Zeng, H., Zhong, Y., Zeng, D., Xiao, S., & Zou, S. (2026). KIAA1429 knockdown alleviates osteosarcoma&nbsp; progression by destabilizing SLC7A11 mRNA via m6A methylation to promote ferroptosis. International Journal of Oncology, 69, 116. https://doi.org/10.3892/ijo.2026.5929
MLA
Zeng, H., Zhong, Y., Zeng, D., Xiao, S., Zou, S."KIAA1429 knockdown alleviates osteosarcoma&nbsp; progression by destabilizing SLC7A11 mRNA via m6A methylation to promote ferroptosis". International Journal of Oncology 69.4 (2026): 116.
Chicago
Zeng, H., Zhong, Y., Zeng, D., Xiao, S., Zou, S."KIAA1429 knockdown alleviates osteosarcoma&nbsp; progression by destabilizing SLC7A11 mRNA via m6A methylation to promote ferroptosis". International Journal of Oncology 69, no. 4 (2026): 116. https://doi.org/10.3892/ijo.2026.5929
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