组蛋白去甲基化酶KDM5A通过LncRNA TRIM52-AS1调控急性髓系白血病的发生和发展

高莉; 李晓明; 杨波; 秦英; 程冬; 郑丽飞; 李里

doi:10.7619/jcmp.20230763

组蛋白去甲基化酶KDM5A通过LncRNA TRIM52-AS1调控急性髓系白血病的发生和发展

高莉¹,
李晓明²,
杨波³,
秦英¹,
程冬¹,
郑丽飞¹,
李里¹

1.
四川省雅安市人民医院血液内科, 四川雅安, 625000
2.
西南医科大学附属医院血液内科, 四川泸州, 646000
3.
四川省攀枝花市中心医院药学部, 四川攀枝花, 617067

基金项目:

云南省科技厅科技计划项目 202001BA070001-178

详细信息

中图分类号: R733.7;R446
计量
- 文章访问数: 145
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出版历程
- 收稿日期: 2023-03-12
- 修回日期: 2023-05-18
- 网络出版日期: 2023-09-18
- 刊出日期: 2023-09-14

Histone demethylase KDM5A regulates the occurrence and development of acute myeloid leukemia through LncRNA TRIM52-AS1

1.
Department of Hematology, Sichuan Ya'an People's Hospital of Sichuan Province, Ya'an, Sichuan, 625000
2.
Department of Hematology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000
3.
Department of Pharmacy, Panzhihua Central Hospital of Sichuan Province, Panzhihua, Sichuan, 617067

摘要

摘要:
目的
初步探索组蛋白去甲基化酶赖氨酸特异性去甲基化酶5(KDM5A)通过长链非编码RNA(LncRNA) TRIM52-AS1调控急性髓系白血病(AML)发生、发展的机制。
方法
通过逆转录定量聚合酶链式反应(qRT-PCR)和蛋白质印迹(Western blot)检测白血病患者血清和各种白血病细胞中的KDM5A、TRIM52-AS1的表达。采用双荧光素酶报告实验检测KDM5A和TRIM52-AS1的靶向关系。通过CCK8实验检测KDM5A和TRIM52-AS1对HL-60细胞增殖的影响。通过Transwell实验检测KDM5A和TRIM52-AS1对HL-60细胞迁移的影响。
结果
KDM5A在白血病患者血清和各种白血病细胞中高表达, TRIM52-AS1在白血病患者血清和各种白血病细胞中低表达(P < 0.05)。KDM5A可以靶向抑制TRIM52-AS1。过表达TRIM52-AS1可以抑制白血病细胞的增殖和迁移, KDM5A可以通过抑制TRIM52-AS1进而抑制白血病细胞的增殖和迁移(P < 0.05)。
结论
组蛋白去甲基化酶KDM5A可通过抑制LncRNA TRIM52-AS1进而抑制AML的发生、发展。
- 赖氨酸特异性去甲基化酶5 /
- 长链非编码RNA TRIM52-AS1 /
- 急性髓系白血病 /
- 增殖 /
- 迁移
Abstract:
Objective
To preliminarily explore the mechanism histone demethylase KDM5A in regulating the occurrence and development of acute myeloid leukemia (AML) through long non-coding RNA (LncRNA) TRIM52-AS1.
Methods
The levels of KDM5A and TRIM52-AS1 were detected by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot in the serum and various leukemia cells of AML patients. The targeting relationship between KDM5A and TRIM52-AS1 was detected by dual luciferase reporter assay. The effects of KDM5A and TRIM52-AS1 on HL-60 cell proliferation were detected by CCK8 assay. The effects ofKDM5A and TRIM52-AS1 on HL-60 cell migration were detected by Transwell assay.
Results
KDM5A was highly expressed in the serum and various leukemia cells of AML patients, while TRIM52-AS1 was lowly expressed (P < 0.05). KDM5A could targetedly inhibit TRIM52-AS1. Overexpression of TRIM52-AS1 could targetedly inhibit leukemia cell proliferation and migration, and KDM5A could inhibit leukemia cell proliferation and migration by inhibiting TRIM52-AS1 (P < 0.05).
Conclusion
Histone demethylase KDM5A can inhibit the occurrence and developmen of AML by inhibiting LncRNA TRIM52-AS1.
- lysine-specific demethylase 5 /
- long non-coding RNA TRIM52-AS1 /
- acute myeloid leukemia /
- proliferation /
- migration

HTML全文

图 1 KDM5A和TRIM52-AS1在白血病细胞中异常表达

A: qRT-PCR检测AML患者的血清中KDM5A mRNA的表达，与正常组比较, *P < 0.05; B: qRT-PCR检测AML患者的血清中
TRIM52-AS1 mRNA的表达，与正常组比较, *P < 0.05; C: qRT-PCR检测白血病细胞中KDM5A和TRIM52-AS1 mRNA的表达，与ARH-77比较, *P < 0.05; D: Western blot检测白血病细胞中KDM5A蛋白的表达。

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图 2 TRIM52-AS1抑制白血病细胞的增殖和迁移

A: qRT-PCR检测TRIM52-AS1的过表达; B: CCK8实验检测过表达TRIM52-AS1后, HL-60细胞的增殖情况; C: Transwell实验检测过表达TRIM52-AS1后, HL-60细胞的迁移情况。与过表达对照组比较, *P < 0.05。所有实验均重复3次。

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图 3 KDM5A靶向抑制TRIM52-AS1

A: qRT-PCR检测KDM5A的敲低效率; B: Western blot检测KDM5A的敲低效率; C: qRT-PCR检测敲低KDM5A后TRIM52-AS1的表达情况; D: 荧光素酶报告实验检测KDM5A对TRIM52-AS1的靶向调控。与敲低对照组比较, *P < 0.05。所有实验均重复3次。

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图 4 KDM5A通过抑制TRIM52-AS1抑制HL-60细胞增殖和迁移

A: qRT-PCR检测各组细胞的KDM5A和TRIM52-AS1表达; B: CCK8实验检测各组细胞增殖;
C: Transwell实验检测各组细胞迁移。两两比较, *P < 0.05。所有实验均重复3次。

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