PDF(Pubmed)
Abstract：
UNASSIGNED: 20(S)-ginsenoside Rh2(GRh2), an effective natural histone deacetylase inhibitor, can inhibit acute myeloid leukemia (AML) cell proliferation. Lactate regulated histone lactylation, which has different temporal dynamics from acetylation. However, whether the high level of lactylation modification that we first detected in acute promyelocytic leukemia (APL) is associated with all-trans retinoic acid (ATRA) resistance has not been reported. Furthermore, Whether GRh2 can regulate lactylation modification in ATRA-resistant APL remains unknown.
UNASSIGNED: Lactylation and METTL3 expression levels in ATRA-sensitive and ATRA-resistant APL cells were detected by Western blot analysis, qRT-PCR and CO-IP. Flow cytometry (FCM) and APL xenograft mouse models were used to determine the effect of METTL3 and GRh2 on ATRA-resistance.
UNASSIGNED: Histone lactylation and METTL3 expression levels were considerably upregulated in ATRA-resistant APL cells. METTL3 was regulated by histone lactylation and direct lactylation modification. Overexpression of METTL3 promoted ATRA-resistance. GRh2 ameliorated ATRA-resistance by downregulated lactylation level and directly inhibiting METTL3.
UNASSIGNED: This study suggests that lactylation-modified METTL3 could provide a promising strategy for ameliorating ATRA-resistance in APL, and GRh2 could act as a potential lactylation-modified METTL3 inhibitor to ameliorate ATRA-resistance in APL.
UNASSIGNED: Lactylation and METTL3 expression levels in ATRA-sensitive and ATRA-resistant APL cells were detected by Western blot analysis, qRT-PCR and CO-IP. Flow cytometry (FCM) and APL xenograft mouse models were used to determine the effect of METTL3 and GRh2 on ATRA-resistance.
UNASSIGNED: Histone lactylation and METTL3 expression levels were considerably upregulated in ATRA-resistant APL cells. METTL3 was regulated by histone lactylation and direct lactylation modification. Overexpression of METTL3 promoted ATRA-resistance. GRh2 ameliorated ATRA-resistance by downregulated lactylation level and directly inhibiting METTL3.
UNASSIGNED: This study suggests that lactylation-modified METTL3 could provide a promising strategy for ameliorating ATRA-resistance in APL, and GRh2 could act as a potential lactylation-modified METTL3 inhibitor to ameliorate ATRA-resistance in APL.
摘要：
■20(S)-人参皂苷Rh2(GRh2),一种有效的天然组蛋白脱乙酰酶抑制剂，能抑制急性髓系白血病(AML)细胞增殖。乳酸盐调节的组蛋白乳酸化，与乙酰化具有不同的时间动力学。然而,我们首次在急性早幼粒细胞白血病(APL)中检测到的高水平的乳酸化修饰是否与全反式维甲酸(ATRA)耐药相关,目前尚无报道.此外，GRh2是否可以调节抗ATRA的APL中的乳酸化修饰仍然未知。
■通过蛋白质印迹分析检测ATRA敏感和抗ATRA的APL细胞中的Lactylation和METTL3表达水平，qRT-PCR和CO-IP。使用流式细胞术(FCM)和APL异种移植小鼠模型来确定METTL3和GRh2对ATRA抗性的影响。
■在抗ATRA的APL细胞中组蛋白乳化作用和METTL3表达水平显著上调。METTL3受组蛋白乳酸化和直接乳酸化修饰调控。METTL3的过表达促进ATRA抗性。GRh2通过下调乳酸化水平和直接抑制METTL3改善ATRA抗性。
■这项研究表明，乳酸盐修饰的METTL3可以为改善APL中的ATRA抗性提供有希望的策略，和GRh2可以作为一种潜在的乳酸化修饰的METTL3抑制剂，以改善APL中的ATRA耐药性。
■通过蛋白质印迹分析检测ATRA敏感和抗ATRA的APL细胞中的Lactylation和METTL3表达水平，qRT-PCR和CO-IP。使用流式细胞术(FCM)和APL异种移植小鼠模型来确定METTL3和GRh2对ATRA抗性的影响。
■在抗ATRA的APL细胞中组蛋白乳化作用和METTL3表达水平显著上调。METTL3受组蛋白乳酸化和直接乳酸化修饰调控。METTL3的过表达促进ATRA抗性。GRh2通过下调乳酸化水平和直接抑制METTL3改善ATRA抗性。
■这项研究表明，乳酸盐修饰的METTL3可以为改善APL中的ATRA抗性提供有希望的策略，和GRh2可以作为一种潜在的乳酸化修饰的METTL3抑制剂，以改善APL中的ATRA耐药性。
