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RAB27B 通过 3-羟基丁酸脱氢酶 2(BDH2)抑制白血病细胞的增殖并促进其凋亡。

RAB27B inhibits proliferation and promotes apoptosis of leukemic cells via 3-Hydroxy butyrate dehydrogenase 2 (BDH2).

机构信息

Department of Hematology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou City, Hainan, China.

出版信息

Bioengineered. 2022 Mar;13(3):5103-5112. doi: 10.1080/21655979.2022.2036903.

DOI:10.1080/21655979.2022.2036903
PMID:35164665
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8973736/
Abstract

RAB27B is a member of Ras-like small GTPases that plays a role in endocytosis, exocytosis, and vesicle trafficking. We made an attempt to study the impacts of RAB27B on the proliferation and apoptosis of acute myeloid leukemia (AML) cells. The silencing of RAB27B was induced by siRNA for the detection of proliferation, cell cycle, and apoptosis, respectively by Cell Counting Kit-8 (CCK8), flow cytometry, and TUNEL. Related markers were also evaluated by Western blot analysis. The interaction between RAB27B and BDH2 was predicted by bioinformatics analysis and determined by immunoprecipitation. The gain of function of BDH2 was also detected by these functional assays. RAB27B exhibited high levels in AML cells, and RAB27B silencing led to reduced proliferation, increased cell cycle arrest and apoptosis levels. Then, the interaction between RAB27B and BDH2 was confirmed. Moreover, the effects of RAB27B inhibition on the proliferation, cell cycle arrest, and cell apoptosis were abolished after BDH2 overexpression. RAB27B inhibits proliferation and promotes apoptosis of leukemic cells by interacting with BDH2. Targeting RAB27B might be an effective method for the treatment of AML.

摘要

RAB27B 是 Ras 样小分子 GTPases 家族的成员,在胞吞作用、胞吐作用和囊泡运输中发挥作用。我们试图研究 RAB27B 对急性髓系白血病(AML)细胞增殖和凋亡的影响。通过 siRNA 沉默 RAB27B,分别通过细胞计数试剂盒-8(CCK8)、流式细胞术和 TUNEL 检测增殖、细胞周期和凋亡。还通过 Western blot 分析评估了相关标记物。通过生物信息学分析预测了 RAB27B 和 BDH2 之间的相互作用,并通过免疫沉淀进行了验证。还通过这些功能测定检测了 BDH2 的功能获得。RAB27B 在 AML 细胞中表达水平较高,沉默 RAB27B 导致增殖减少、细胞周期阻滞和凋亡水平增加。然后,确认了 RAB27B 和 BDH2 之间的相互作用。此外,BDH2 过表达后,RAB27B 抑制对增殖、细胞周期阻滞和细胞凋亡的影响被消除。RAB27B 通过与 BDH2 相互作用抑制白血病细胞的增殖并促进其凋亡。靶向 RAB27B 可能是治疗 AML 的有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/8973736/c971cfca0e42/KBIE_A_2036903_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/8973736/104ae645d46a/KBIE_A_2036903_UF0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/8973736/5638c88e2fc6/KBIE_A_2036903_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/8973736/c497aeab2ff0/KBIE_A_2036903_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/8973736/cd41440d0011/KBIE_A_2036903_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/8973736/6a9f99ff3ee1/KBIE_A_2036903_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/8973736/2b41347c4b60/KBIE_A_2036903_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/8973736/c971cfca0e42/KBIE_A_2036903_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/8973736/104ae645d46a/KBIE_A_2036903_UF0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/8973736/5638c88e2fc6/KBIE_A_2036903_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/8973736/c497aeab2ff0/KBIE_A_2036903_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/8973736/cd41440d0011/KBIE_A_2036903_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/8973736/6a9f99ff3ee1/KBIE_A_2036903_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/8973736/2b41347c4b60/KBIE_A_2036903_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/8973736/c971cfca0e42/KBIE_A_2036903_F0006_OC.jpg

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