MicroRNA-141-5p/ABCG1逆转慢性粒细胞白血病K562细胞对伊马替尼的耐药性  

MicroRNA-141-5p/ABCG1 reverses imatinib resistance in K562 chronic myeloid leukemia cells

作　　者：许晗 许婷婷 汪万杰 鲍静[1] Xu Han;Xu Tingting;Wang Wanjie;Bao Jing(Dept of Hematology,Affiliated Hospital of Anhui Medical University,Hefei230022)

机构地区：[1]安徽医科大学第一附属医院血液内科,合肥230022

出　　处：《安徽医科大学学报》2024年第11期1887-1896,共10页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金项目(编号:2008085MH296);安徽医科大学科学研究基金项目(编号:2020xkj186);安徽省教育厅高校科研计划重点项目(编号:2022AH051178)。

摘　　要：目的探究miR-141-5p在慢性粒细胞白血病(CML)的作用机制及其对甲磺酸伊马替尼(IM)耐药性的影响。方法qRT-PCR检测IM耐药和敏感患者miR-141-5p mRNA水平;Western blot法分别检测K562和K562/G01细胞转染前后MMP-3、MMP-9、Bcl-2等蛋白的表达情况;CCK-8检测K562和K562/G01细胞活性;荧光素酶实验检测miR-141-5p与ABCG1的结合情况;裸鼠成瘤验证miR-141-5p在体内对肿瘤的影响。结果miR-141-5p在IM耐药的CML患者和K562/G01细胞中下调,且miR-141-5p的过表达可以抑制IM耐药CML细胞的生长并促进其凋亡。对荷瘤小鼠的研究表明,miR-141-5p在体内抑制肿瘤生长。miR-141-5p可以直接靶向作用于IM耐药CML细胞中的ABCG1调控CML发生。结论miR-141-5p和ABCG1形成竞争性内源性RNA(ceRNA)网络,在IM耐药性中发挥作用,从而抑制CML的进展。Objective To explore the mechanism of miR-141-5p and its effect on Imatinib(IM)resistance in CML.Methods qRT-PCR was used to detect miR-141-5p mRNA levels in IM resistant and sensitive patients.Western blot was used to detect the expression of proteins such as MMP-3,MMP-9,and Bcl-2 before and after transfection in K562 and K562/G01 cells.CCK-8 was used to detect of K562 and K562/G01 cell activity;Flow cytometry assay was used to detect the binding of miR-141-5p with ABCG1;Nude mice were used to validate the effect of miR-141-5p on tumors in vivo.Results The results showed that miR-141-5p was downregulated in IM-resistant CML patients and IM-resistant CML cells and overexpression of miR-141-5p could inhibit the growth of IM-resistant CML cells and promote their apoptosis.Research on tumor bearing mice had shown that miR-141-5p inhibits tumor growth in vivo.Finally,it was found that miR-141-5p could directly target ABCG1 in IM-resistant CML cells to regulate CML occurrence.Conclusion miR-141-5p and ABCG1 form a competing endogenous RNA(ceRNA)network to function in IM resistance,thus facilitating CML progression.

关 键 词：慢性粒细胞白血病 miR-141-5p 伊马替尼 ABCG1 耐药 K562 

分 类 号：R733.7[医药卫生—肿瘤]