MiRNA-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with MLL gene rearrangement by targeting STYX

Rui YANG; Jing NING; Lijuan JING; Hainan WANG; Lijuan CUI

doi:10.16016/j.1000-5404.202105091

您当前的位置：

首页 >

文章列表页 >

MiRNA-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with MLL gene rearrangement by targeting STYX

Basic Medicine | 更新时间：2026-01-09

- MiRNA-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with MLL gene rearrangement by targeting STYX
- Journal of Third Military Medical University Vol. 43, Issue 22, Pages: 2407-2413(2021)
- 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：
- 基金信息：
  
  the General Project of Ningxia Medical University(XM2019089)
- DOI：10.16016/j.1000-5404.202105091
  CLC： R394.3;R730.23;R733.71
- Received：21 May 2021，
  
  Revised：2021-06-02，
  
  Published：30 November 2021
- 稿件说明：
移动端阅览
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：

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

颜金花. miR-217在急性髓系白血病中的临床意义及其机制研究[D]. 南昌: 南昌大学, 2019.

YAN J H. Clinical significance and mechanism of miR-217 in acute myeloid leukemia[D]. Nanchang: Nanchang University, 2019.

刘之茵, 张苏江, 陈玉宝, 等. MLL基因重排在急性白血病亚型分布及疗效分析[J]. 临床血液学杂志, 2021, 34(3): 177-181. DOI: 10.13201/j.issn.1004-2806.2021.03.007.

LIU Z Y, ZHANG S J, CHEN Y B, et al . Distribution and efficacy of MLL gene rearrangement in acute leukemia subtypes[J ] . J Clin Hematol, 2021, 34(3): 177-181. DOI: 10.13201/j.issn.1004-2806.2021.03.007.

李昱瑛. MLL重排白血病人源化小鼠模型的建立及系别转换的研究[D]. 长春: 吉林大学, 2017.

LI Y Y. Establishment of humanized mouse model of MLL rearranged leukemias and lineage switch determination[D]. Changchun: Jilin University, 2017.

余梦霞. miR-320c在急性髓系白血病中的临床意义及其机制研究[D]. 杭州: 浙江大学, 2017.

YU M X. The clinical significance and mechanism of miR-320c in acute myeloid leukemia[D]. Hangzhou: Zhejiang University, 2017.

胡超. miR-550-1在急性髓系白血病中的抑癌作用及其机制研究[D]. 杭州: 浙江大学, 2016.

HU C. The anti-tumor function and mechanism of miR-550-1 in acute myeloid leukemia[D]. Hangzhou: Zhejiang University, 2016.

CHU H Y, CHEN X D, WANG H Q, et al . MiRNA-495 regulates proliferation and migration in NSCLC by targeting MTA3[J ] . Tumor Biol, 2014, 35(4): 3487-3494. DOI: 10.1007/s13277-013-1460-1.

NIE S, LI K Q, HUANG Y, et al . MiRNA-495 mediates metabolic shift in glioma cells via targeting Glut1[J ] . J Craniofacial Surg, 2015, 26(2): e155-e158. DOI: 10.1097/SCS.0000000000001385.

HWANG-VERSLUES W W, CHANG P H, WEI P C, et al . MiRNA-495 is upregulated by E12/E47 in breast cancer stem cells, and promotes oncogenesis and hypoxia resistance via downregulation of E-cadherin and REDD1[J ] . Oncogene, 2011, 30(21): 2463-2474. DOI: 10.1038/onc.2010.618.

LI Z, ZHANG G, LI D, et al . Methylation-associated silencing of miRNA-495 inhibit the migration and invasion of human gastric cancer cells by directly targeting PRL-3[J ] . Biochem Biophys Res Commun, 2015, 456(1): 344-350. DOI: 10.1016/j.bbrc.2014.11.083.

叶敏婷. miRNA-495调控TSPAN12在小细胞肺癌耐药和增殖中的作用研究[D]. 广州: 南方医科大学, 2015.

YE M T. Investigation of role for TSPAN12 in chemoresistance and proliferation of SCLC under regulation of miRNA-495[D]. Guangzhou: Southern Medical University, 2015.

王娜. MiR-34b在儿童急性白血病中的表达、甲基化调控及临床意义的研究[D]. 苏州: 苏州大学, 2013.

WANG N. The expression, methylated regulation and clinical significances of miR-34b in pediatric acute leukemia[D]. Suzhou: Soochow University, 2013.

吕蔡. miRNA-495靶向SATB1基因对肾细胞癌调控作用的研究[D]. 武汉: 武汉大学, 2015.

LYU C. MicroRNA-495 suppresses human renal cell carcinoma malignancy by targeting SATB1[D]. Wuhan: Wuhan University, 2015.

刘静. MLL-AF6、MLL-AF9及MLL-AF10与急性髓系白血病的临床研究[D]. 合肥: 安徽医科大学, 2015.

LIU J. The clinical study of MLL-AF6, MLL-AF9 and MLL-AF10 In acute myeloid leukemia[D]. Hefei: Anhui Medical University, 2015.

郑华峰, 陶晶, 张斌, 等. miRNA-495通过下调PCNA抑制人血管内皮细胞增殖的作用研究[J]. 中国心血管病研究, 2016(4): 374-379. DOI: 10.3969/j.issn.1672-5301.2016.04.023.

ZHENG H F, TAO J, ZHANG B, et al . MiRNA-495 inhibits human vascular endothelial cells proliferation by down-regulating PCNA[J ] . Chin J Cardiouasc Res, 2016, 14(004): 374-379. DOI: 10.3969/j.issn.1672-5301.2016.04.023.

张帆, 余国玺, 王力锋. miRNA-495-3p对LPS刺激人牙周膜细胞增殖及炎性因子表达的影响[J]. 口腔生物医学, 2017, 8(2): 86-89. DOI: 10.3969/j.issn.1674-8603.2017.02.007.

ZHANG F, YU G X, WANG L F. Effect of miRNA-495-3p onthe proliferation of hPDLC and the production of inflammatory cytokines induced by LPS[J]. Oral Biomed, 2017, 8(2): 86-89. DOI: 10.3969/j.issn.1674-8603.2017.02.007.

TOMAR V S, BARAL T K, NAGAVELU K, et al . Serine/threonine/tyrosine-interacting-like protein 1 (STYXL1), a pseudo phosphatase, promotes oncogenesis in glioma[J ] . Biochem Biophys Res Commun, 2019, 515(1): 241-247. DOI: 10.1016/j.bbrc.2019.05.093.

HE D, MA Z, FANG C, et al . Pseudophosphatase STYX promotes tumor growth and metastasis by inhibiting FBXW7 function in colorectal cancer[J ] . Cancer Lett, 2019, 454: 53-65. DOI: 10.1016/j.canlet.2019.04.014.

REITERER V, FIGUERAS-PUIG C, LE GUERROUE F, et al . The pseudophosphatase STYX targets the F-box of FBXW7 and inhibits SCFFBXW7 function[J ] . EMBO J, 2017, 36(3): 260-273. DOI: 10.15252/embj.201694795.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Promoting effect of ultra-low dose DMSO on fibroblast proliferation and its underlying mechanism

Impact of molecular heterogeneity of NPM1 mutations on prognosis of acute myeloid leukemia: a clinical report of 86 cases

GPX7 regulates proliferation and senescence of hepatocellular carcinoma cells through the PI3K-AKT pathway

Mechanism of abnormal specification of spermatogonial stem cells after Rb1 knockout in mitotic-arrested prospermatogonia

Related Author

TAN Ranjing

KANG Tehao

WU Dengyan

YU Xiaoda

GUO Jiangang

WANG An’an

LI Jiajing

LIU Bei

Related Institution

Center for Dermatology and Medical Cosmetology， the Second Affiliated Hospital of Chongqing Medical University

Department of Dermatology， Plastic and Cosmetic Surgery， Wushan People’s Hospital

the First Clinical Medical College of Lanzhou University, the First Hospital of Lanzhou University

Department of Hematology, the First Hospital of Lanzhou University

Faculty of Hepatobiliary and Pancreatic Surgery， First Medical Center， General Hospital of PLA， Beijing, Air Force Medical Center of PLA

⁰