miRNA-495靶向STYX调节MLL-AF9的急性髓系白血病细胞的增殖和凋亡

杨瑞; 宁婧; 景丽娟; 王海楠; 崔丽娟

doi:10.16016/j.1000-5404.202105091

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miRNA-495靶向STYX调节MLL-AF9的急性髓系白血病细胞的增殖和凋亡

基础医学 | 更新时间：2026-01-09

- miRNA-495靶向STYX调节MLL-AF9的急性髓系白血病细胞的增殖和凋亡
- MiRNA-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with MLL gene rearrangement by targeting STYX
- 第三军医大学学报 2021年43卷第22期页码：2407-2413
- 作者机构：
  
  1.750004 银川，宁夏医科大学总医院血液科
  2.750004 银川，宁夏医科大学总医院医学实验中心
- 作者简介：
  
  [ 崔丽娟，E-mail：cuilijuan7511@163.com CUI Lijuan, E-mail: cuilijuan7511@163.com
- 基金信息：
  
  宁夏医科大学校级课题一般项目(XM2019089)
- DOI：10.16016/j.1000-5404.202105091
  中图分类号： R394.3;R730.23;R733.71
- 收稿：2021-05-21，
  
  修回：2021-06-02，
  
  纸质出版：2021-11-30
- 稿件说明：
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杨瑞, 宁婧, 景丽娟, 等. miRNA-495靶向STYX调节MLL-AF9的急性髓系白血病细胞的增殖和凋亡[J]. 第三军医大学学报, 2021,43(22):2407-2413.

Rui YANG, Jing NING, Lijuan JING, et al. MiRNA-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with MLL gene rearrangement by targeting STYX[J]. Journal of Third Military Medical University, 2021, 43(22): 2407-2413.
杨瑞, 宁婧, 景丽娟, 等. miRNA-495靶向STYX调节MLL-AF9的急性髓系白血病细胞的增殖和凋亡[J]. 第三军医大学学报, 2021,43(22):2407-2413. DOI： 10.16016/j.1000-5404.202105091.

Rui YANG, Jing NING, Lijuan JING, et al. MiRNA-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with MLL gene rearrangement by targeting STYX[J]. Journal of Third Military Medical University, 2021, 43(22): 2407-2413. DOI： 10.16016/j.1000-5404.202105091.

摘要

目的

探究miRNA-495对混合谱系白血病基因(mixed lineage leukemia

MLL)基因重排的急性髓系白血病（acute myeloid leukemia，AML）增殖和凋亡的影响。

方法

收集2017年8月至2019年5月于宁夏医科大学总医院血液科就医确诊为AML的10例MLL-AF9白血病患者[男性6例，女性4例，年龄（39.37±2.71）岁]；10例急性髓系白血病患者[男性5例，女性5例，年龄（41.12±1.92）岁]；同时间段于外科门诊就医患者10例[男性6例，女性4例，年龄（42.31±3.21）岁]。根据是否转染miRNA-495 mimic分组为miRNA-495组和Control组，通过RT-qPCR检测各组miRNA-495的表达；CCK-8检测各组转染THP-1细胞的增殖情况；RT-qPCR和Western blot检测各组转染THP-1细胞增殖相关因子（Ki-67和PCNA）和细胞凋亡相关因子（Bcl-2、Bax和Caspase-3）的表达；TargetScan预测miRNA-495的靶基因并用双荧光素酶报告实验验证；RT-qPCR和Western blot检测miRNA-495组(转染miRNA-495)、Control组、丝氨酸/苏氨酸/酪氨酸相互作用蛋白（Serine/threonine/tyrosine interacting protein，STYX）组（转染STYX）和miRNA-495+STYX组（转染miRNA-495和STYX）中STYX的表达。

结果

miRNA-495在MLL-AF9的AML患者中表达下调[MLL-AF9患者相对表达量（0.25±0.08），95%CI：-0.86~-0.65，

0.01，

0.001

]

；miRNA-495可以抑制THP-1细胞增殖（

0.05，

0.01，

0.001）；miRNA-495可以诱导THP-1细胞的凋亡（

0.05，

0.001）；miRNA-495靶向结合STYX（

0.01，

0.001）；STYX过表达可以逆转miRNA-495对THP-1细胞增殖和凋亡的作用（

0.05，

0.01，

0.001）。

结论

miRNA-495通过靶向STYX调控MLL基因重排的急性髓系白血病细胞的增殖和凋亡。

Abstract

Objective

To investigate the effect of miRNA-495 on the proliferation and apoptosis of acute myeloid leukemia (AML) cells with mixed lineage leukemia (MLL) gene rearrangement.

Methods

Ten patients diagnosed with AML with MLL-AF9 fusion gene positive (6 males

4 females

mean age of 39.37±2.71 years)

and 10 cases of AML (5 males

5 females

mean age of 41.12±1.92 years) admitted in our hospital from August 2017 to May 2019 were enrolled in this study

and another 10 patients (6 males

4 females

mean age of 42.31±3.21 years) who attended the surgical outpatient department during the same period were also collected as the control. THP-1 cells (containing MLL-AF9 fusion gene) were divided into miRNA-495 and control groups based on transfection with miRNA-495 or not

and the expression of miRNA-495 in each group was detected by RT-qPCR; CCK-8 assay was used to determine the proliferation of transfected THP-1 cells in each group; RT-qPCR and Western blotting were performed to measure the expression of proliferation-related factors (Ki-67 and PCNA) and apoptosis-related factors (Bcl-2

Bax and Caspase-3). The target genes of miRNA-495 were predicted by TargetScan and then verified by dual-luciferase reporter assay. Finally

RT-qPCR and Western blotting were adopted to detect the expression of serine/threonine/tyrosine interacting protein (STYX) in groups as follows: miRNA-495 group

control group

STYX group (transfected with STYX) and miRNA-495+STYX group (transfected with miRNA-495 and STYX).

Results

MiRNA-495 expression was down-regulated in AML patients with MLL-AF9 fusion gene

with relative expression of 0.25±0.08 (95%

=-0.86~-0.65

0.001); miRNA-495 inhibited cell proliferation (

0.001) and induced apoptosis of THP-1 cells

and it targetedly bound to STYX (

0.001). In addition

STYX overexpression reversed the effects of miRNA-495 on THP-1 cell proliferation and apoptosis.

Conclusion

MiRNA-495 regulates the proliferation and apoptosis of AML cells with MLL gene rearrangement by targeting STYX.

关键词

Keywords

references

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