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

Published in

International journal of oncology. Volume 69. Issue 4. Epub Aug 21, 2026.

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.

PMID:
42627048
Bibliographic data and abstract were imported from PubMed on 21 Aug 2026.

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