内科理论与实践2025，Vol.20Issue(2)：146-151,6.DOI:10.16138/j.1673-6087.2025.02.08
PML::RARα融合蛋白对白介素6受体的转录调控研究
Transcriptional regulation of interleukin-6 receptor by PML::RARα fusion protein
摘要
Abstract
Objective To investigate the regulatory mechanism of PML::RARα fusion protein on interleukin-6 receptor(IL-6R)and the effects of IL-6R on the proliferation and differentiation of acute promyelocytic leukemia(APL)cells.Methods The expression levels of IL-6R in APL cells were analyzed using the GSE12662 and GSE10358 datasets.Reverse transcription quantitative real-time quantitative PCR(RT-qPCR)was performed to detect IL-6R mRNA expression in NB4 cells before and after all-trans retinoic acid(ATRA)treatment,as well as in PR9 cells before and after Zn2+induction.Chromatin immunoprecipitation(ChIP)-seq data analysis,ChIP-qPCR experiments,and luciferase reporter gene activity assays were performed to explore the regulatory mechanism of PML::RARα on IL-6R.An IL-6R expression plasmid was constructed for NB4 cells via retrovirus.Cell proliferation was assessed using the cell counting kit-8(CCK-8)assay,and CD11b expression was detected by flow cytometry.Results Analysis of the GSE12662 dataset revealed that the expression level of IL-6R in APL cells(12.20±0.41)was significantly lower than that in normal promyelocytes(13.14±0.47,t=4.289,P<0.001)and polymorphonuclear cells(14.82±0.40,t=12.35,P<0.001).Moreover,analysis of the GSE10358 dataset showed that IL-6R expression in APL patients(5.93±0.84)was significantly lower than that in non-APL AML patients(6.50±0.87,t=3.91,P<0.001).PML::RARα directly bound to the promoter region of IL-6R to inhibit its transcriptional activity resulting in the low expression.Overexpression of IL-6R in the APL-derived NB4 cells significantly inhibited cell proliferation.Four days after transfection,the optical density values measured by the CCK-8 assay were 0.86±0.01 and 0.40±0.01,respectively(t=32.66,P<0.001).Simultaneously,cell differentiation was significantly enhanced.The ratio of the CD11b positive cells increased from 3.10％±1.22％to 14.4％±1.11％(t=11.84,P<0.001).Conclusions IL-6R is a target gene of PML::RARα,demonstrating that PML::RARα can suppress IL-6R transcription by binding to its promoter region.It is illustrated that IL-6R inhibited the cell proliferation and induced partial differentiation in APL cells.关键词
白介素6受体/急性早幼粒细胞白血病/PML::RARα/细胞增殖/细胞分化Key words
Interleukin-6 receptor/Acute promyelocytic leukemia/PML::RARα/Cell proliferation/Cell differentiation分类
医药卫生引用本文复制引用
赵玲玲,崔灿琦,糜坚青..PML::RARα融合蛋白对白介素6受体的转录调控研究[J].内科理论与实践,2025,20(2):146-151,6.基金项目
国家重点研发计划(2023YFC2508900) （2023YFC2508900）
上海交通大学医学院"上海市高水平地方高校"协同创新团队项目 （）
