N6-Methyladenosine modification mediated by METTL3 promotes DNA-PKcs expression to induce anlotinib resistance in osteosarcoma

Yining Zhang; Guohong Shen; Dan Zhang; Tingting Meng; Zhaorui Lv; Lei Chen; Jianmin Li; Ka Li

doi:10.1002/ctm2.70228

Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (2) : e70228 DOI: 10.1002/ctm2.70228

RESEARCH ARTICLE

N⁶-Methyladenosine modification mediated by METTL3 promotes DNA-PKcs expression to induce anlotinib resistance in osteosarcoma

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Abstract

	•DNA-PKcs knockdown heightens osteosarcoma sensitivity to anlotinib.
	•DNA-PKcs modulates anlotinib-induced protective autophagy through interacts with Beclin-1 and regulates its ubiquitination.
	•m⁶A modification of OLE_LINK82PRKDC mRNA induced by METTL3 contributes to anlotinib resistance in osteosarcoma.
	•m⁶A methylation of PRKDC mRNA recognised by YTHDF1 amplifies the expression of DNA-PKcs.

Keywords

anlotinib / DNA-PKcs / m ⁶A / METTL3 / osteosarcoma

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Yining Zhang,Guohong Shen,Dan Zhang,Tingting Meng,Zhaorui Lv,Lei Chen,Jianmin Li,Ka Li. N⁶-Methyladenosine modification mediated by METTL3 promotes DNA-PKcs expression to induce anlotinib resistance in osteosarcoma. Clinical and Translational Medicine, 2025, 15(2): e70228 DOI:10.1002/ctm2.70228

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2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.