中国医学科学院学报2025，Vol.47Issue(3)：333-342,10.DOI:10.3881/j.issn.1000-503X.16246
YTH结构域家族蛋白2对亚砷酸钠诱导皮肤细胞恶性转化的影响
Effect of YTH Domain Family Protein 2 on the Sodium Arsenite-Induced Malignant Transformation of Skin Cells
摘要
Abstract
Objective To investigate the effect of liquid-liquid phase separation(LLPS)of YTH domain family protein 2(YTHDF2)on the sodium arsenite-induced malignant transformation of skin cells,pro-viding a new intervention target for the prevention and control of sodium arsenite-induced carcinogene-sis.Methods The HaCaT cell model of malignant transformation was constructed by continuous treatment with 1 μmol/L sodium arsenite for 22 weeks,including cells with normal YTHDF2 LLPS(YTHDF2-wt)and cells with inhibited YTHDF2 LLPS(YTHDF2-mut).Confocal microscopy was employed to observe and characterize the LLPS droplets formed by YTHDF2 during sodium arsenite-induced malignant transformation of skin cells.Cell proliferation,scratch healing,and colony formation assays were performed to detect malignant pheno-types.Western blotting,quantitative reverse transcription PCR,and immunofluorescence experiments were con-ducted to examine the effects of YTHDF2 LLPS on the mRNA and protein levels of phosphatase and tensin homo-log deleted on chromosome ten(PTEN)during sodium arsenite-induced malignant transformation of skin cells.Results After 4 weeks of sodium arsenite treatment,LLPS droplets of YTHDF2 appeared in YTHDF2-wt cells,and the number of droplets gradually increased as the treatment time was prolonged(F=35.252,P＜0.001),while no phase-separated droplets were observed in YTHDF2-mut cells.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed enhanced proliferation at the time points of 48 h(t=3.654,P=0.006)and 72 h(t=5.458,P＜0.001)after 22 weeks of sodium arsenite treatment.The scratch healing rate of YTHDF2-wt cells was increased at the 8th(t=12.137,P＜0.001)and 22th(t=4.484,P=0.011)weeks of sodi-um arsenite treatment.The number of colonies formed by YTHDF2-wt cells was higher at the 4th(t=3.365,P=0.027),8th(t=5.580,P=0.005),and 22th(t=3.328,P=0.029)weeks of sodium arsenite treat-ment.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed down-regulated protein(t=-3.119,P=0.036)and mRNA(t=4.051,P=0.015)levels of PTEN after 22 weeks of sodium arsenite treatment.Immunofluorescence results showed that after 4 weeks of sodium arsenite treatment,YTHDF2 LLPS droplets in YTHDF2-wt cells were localized to stress granules,translation-related membrane-less organelles.Conclusions During sodium arsenite-induced malignant transformation of skin cells,YTHDF2 undergoes LLPS and localizes to stress granules,translation-related membrane-less organelles.YTHDF2 LLPS participates in sodium arsenite-in-duced malignant transformation of skin cells by down-regulating the mRNA level of the key tumor suppressor PTEN.关键词
YTH结构域家族蛋白2/相分离/第10号染色体缺失的磷酸酶和张力蛋白同源物/亚砷酸钠/恶性转化Key words
YTH domain family protein 2/phase separation/phosphatase and tensin homolog deleted on chromosome ten/so-dium arsenite/malignant transformation分类
医药卫生引用本文复制引用
熊文晓,赵田禾,龙科言,张遵真..YTH结构域家族蛋白2对亚砷酸钠诱导皮肤细胞恶性转化的影响[J].中国医学科学院学报,2025,47(3):333-342,10.基金项目
国家自然科学基金(82073510) （82073510）
