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A B C
1.5 shRNA⁃NC MDA⁃MB⁃231 HCC⁃1806 MDA⁃MB⁃231 HCC⁃1806
shIGF2BP3⁃1
shIGF2BP3⁃2 shRNA⁃NC shIGF2BP3⁃1 shIGF2BP3⁃2 shRNA⁃NC shIGF2BP3⁃1 shIGF2BP3⁃2 shRNA⁃NC shIGF2BP3⁃1 shIGF2BP3⁃2 shRNA⁃NC shIGF2BP3⁃1 shIGF2BP3⁃2
Relative IGF2BP3 mRNA expression 0.5 * * IGF2BP3 69 kDa
1.0

*
42 kDa
β⁃ACTIN
*
Pan⁃Kla
0
MDA⁃MB⁃231 HCC⁃1806 -15 kDa

Histone H3 -15 kDa
A：RT⁃qPCR was used to detect the relative expression levels of IGF2BP3 in triple⁃negative breast cancer cell lines after lentivirus⁃mediated
*
knockdown. Compared to the shRNA ⁃ NC group，P < 0.05. B：Western blot analysis was performed to validate the knockdown efficiency of
IGF2BP3 at the protein level. C：Western blot analysis of global histone lactylation levels following IGF2BP3 knockdown（n=3）.
图3 IGF2BP3的敲低抑制了TNBC细胞的组蛋白乳酸化
Figure 3 Knockdown of IGF2BP3 inhibits histone lactylation in TNBC cells
A B
GO results of three ontologies 10 kb
Protein folding
Protein localization to nucleus Input⁃RIP⁃seq⁃1
Establishment of protein localization to organelle
BP Input⁃RIP⁃seq⁃2
Positive regulation of establishment
of protein localization to telomere CC RIP⁃seq⁃1
Positive regulation of DNA biosynthetic process MF
Regulation of establishment of RIP⁃seq⁃2
protein localization to telomere
Regulation of protein localization to Cajal body Input⁃MeRIP⁃seq⁃1
Positive regulation of protein localization to Cajal body
Input⁃MeRIP⁃seq⁃2
Regutation of establishment of
protein localization to chromoseome
MeRIP⁃seq⁃1
Protein localization to nuclear body
Melancsome MeRIP⁃seq⁃2
Pigment granule
Chaperone complex
Ficolin⁃1⁃rich granule lumen
EP300
Ficolin⁃1⁃rich granule
Chaperonin⁃containing T⁃complex
Secretory granule lumen
Cytoplasmic vesicle lumen
Vesicle lumen
Focal adhesion
Uniolded protein binding
Proein foiding chaperone
ATP hydrolysis activity
Nuclear localization sequence binding
Cadherin binding
Helicase activity
Histone deacetvlase binding
Nuclear import signal receptor activity
Signal sequence binding
Nucleocytoplasmic carrier activity
0 5 10 15
Enrichment score
A：GO analysis indicates that these genes are significantly enriched in pathways related to epigenetic regulation and metabolic reprogram⁃
ming. B：The mRNA of EP300 has multiple high⁃confidence binding sites for IGF2BP3，which overlap significantly with m6A modification motifs.
图4 IGF2BP3通过介导EP300的m6A修饰调控表观遗传与代谢重编程
Figure 4 IGF2BP3 regulates epigenetics and metabolic reprogramming through m6A modification of EP300