BCLAF1 对 HDAC 抑制剂 LMK-235 介导的弥漫性大 B 细胞淋巴瘤细胞凋亡的影响及其机制。
Effect of BCLAF1 on HDAC inhibitor LMK-235-mediated apoptosis of diffuse large B cell lymphoma cells and its mechanism.
机构信息
a Guizhou Medical University , Guiyang , Guizhou , China.
d Guizhou Province Laboratory of Haematopoietic Stem Cell Transplantation Center , Guiyang , Guizhou , China.
出版信息
Cancer Biol Ther. 2018;19(9):825-834. doi: 10.1080/15384047.2018.1472188. Epub 2018 Jul 3.
Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common type of adult lymphoma. It is a group of malignant tumors with a large number of clinical manifestations and prognoses. Therefore, it is necessary to explore its unknown potential therapeutic targets. Histone deacetylase inhibitor (HDACi) is a novel drug for the treatment of DLBCL, however pan-HDACis cannot be ignored because of their clinical efficacy. By contrast, specific HDACi is well-tolerated, and LMK-235 is a novel HDACi that is a specific inhibitor of HDAC4 and HDAC5. In this study, we investigated the up-regulation of BCLAF1 through NF-κB signaling pathways in LMK-235, mediating the apoptosis of two diffuse large B-cell lymphoma cell lines, OCI-LY10 and OCI-LY3. Further studies showed that BCLAF1 expression was increased in DLBCL cells after treatment with the NF-κB inhibitor Bay11-7082. The combination of Bay11-7082 and siRNA si-HDAC4 significantly increased BCLAF1 expression and further increased apoptosis. These results indicate that BCLAF1 plays an important role in LMK-235-mediated apoptosis and may be a potential target for the treatment of diffuse large B-cell lymphoma.
摘要
弥漫性大 B 细胞淋巴瘤（DLBCL）是成人淋巴瘤中最常见的类型。它是一组临床表现和预后差异较大的恶性肿瘤。因此，有必要探索其未知的潜在治疗靶点。组蛋白去乙酰化酶抑制剂（HDACi）是治疗 DLBCL 的新型药物，但 pan-HDACi 因其临床疗效而不容忽视。相比之下，特异性 HDACi 具有良好的耐受性，而 LMK-235 是一种新型的 HDACi，它是 HDAC4 和 HDAC5 的特异性抑制剂。在这项研究中，我们通过 NF-κB 信号通路研究了 LMK-235 上调 BCLAF1 在两种弥漫性大 B 细胞淋巴瘤细胞系 OCI-LY10 和 OCI-LY3 中的作用，介导其凋亡。进一步的研究表明，NF-κB 抑制剂 Bay11-7082 处理后，DLBCL 细胞中 BCLAF1 的表达增加。Bay11-7082 和 siRNA si-HDAC4 的联合使用显著增加了 BCLAF1 的表达，并进一步增加了细胞凋亡。这些结果表明，BCLAF1 在 LMK-235 介导的凋亡中起重要作用，可能是治疗弥漫性大 B 细胞淋巴瘤的潜在靶点。
相似文献
1
Effect of BCLAF1 on HDAC inhibitor LMK-235-mediated apoptosis of diffuse large B cell lymphoma cells and its mechanism.BCLAF1 对 HDAC 抑制剂 LMK-235 介导的弥漫性大 B 细胞淋巴瘤细胞凋亡的影响及其机制。
Cancer Biol Ther. 2018;19(9):825-834. doi: 10.1080/15384047.2018.1472188. Epub 2018 Jul 3.
2
Up-regulation of HO-1 promotes resistance of B-cell acute lymphocytic leukemia cells to HDAC4/5 inhibitor LMK-235 via the Smad7 pathway.HO-1 的上调通过 Smad7 通路促进 B 细胞急性淋巴细胞白血病细胞对 HDAC4/5 抑制剂 LMK-235 的耐药性。
Life Sci. 2018 Aug 15;207:386-394. doi: 10.1016/j.lfs.2018.06.004. Epub 2018 Jun 7.
3
AUY922 effectively targets against activated B cell subtype of diffuse large B-cell lymphoma and low-grade lymphoma cells harboring genetic alteration-associated nuclear factor-κB activation.AUY922可有效靶向弥漫性大B细胞淋巴瘤的活化B细胞亚型以及携带与核因子κB激活相关基因改变的低度淋巴瘤细胞。
Leuk Lymphoma. 2015;56(9):2674-82. doi: 10.3109/10428194.2014.995647. Epub 2015 Jan 21.
4
Novel HDAC inhibitor Chidamide synergizes with Rituximab to inhibit diffuse large B-cell lymphoma tumour growth by upregulating CD20.新型 HDAC 抑制剂西达本胺通过上调 CD20 与利妥昔单抗协同抑制弥漫大 B 细胞淋巴瘤肿瘤生长。
Cell Death Dis. 2020 Jan 6;11(1):20. doi: 10.1038/s41419-019-2210-0.
5
Histone deacetylase inhibitor LMK-235-mediated HO-1 expression induces apoptosis in multiple myeloma cells via the JNK/AP-1 signaling pathway.组蛋白去乙酰化酶抑制剂 LMK-235 通过 JNK/AP-1 信号通路诱导多发性骨髓瘤细胞发生凋亡，HO-1 表达上调。
Life Sci. 2019 Apr 15;223:146-157. doi: 10.1016/j.lfs.2019.03.011. Epub 2019 Mar 12.
6
Overexpression of heme oxygenase-1 induced by constitutively activated NF-κB as a potential therapeutic target for activated B-cell-like diffuse large B-cell lymphoma.NF-κB 持续激活诱导血红素加氧酶-1 过表达作为激活 B 细胞样弥漫大 B 细胞淋巴瘤的潜在治疗靶点。
Int J Oncol. 2016 Jul;49(1):253-64. doi: 10.3892/ijo.2016.3529. Epub 2016 May 17.
7
Pharmacological Inhibition of Class IIA HDACs by LMK-235 in Pancreatic Neuroendocrine Tumor Cells.LMK-235 对胰腺神经内分泌肿瘤细胞的 IIA 类组蛋白去乙酰化酶的抑制作用。
Int J Mol Sci. 2018 Oct 12;19(10):3128. doi: 10.3390/ijms19103128.
8
Low dose of lenalidmide and PI3K/mTOR inhibitor trigger synergistic cytoxicity in activated B cell-like subtype of diffuse large B cell lymphoma.低剂量来那度胺与PI3K/mTOR抑制剂在弥漫性大B细胞淋巴瘤活化B细胞样亚型中引发协同细胞毒性。
J Exp Clin Cancer Res. 2016 Mar 24;35:52. doi: 10.1186/s13046-016-0327-x.
9
A model of sensitivity and resistance to histone deacetylase inhibitors in diffuse large B cell lymphoma: Role of cyclin-dependent kinase inhibitors.弥漫性大 B 细胞淋巴瘤中组蛋白去乙酰化酶抑制剂敏感性和耐药性的模型：细胞周期蛋白依赖性激酶抑制剂的作用。
Cancer Biol Ther. 2013 Oct 1;14(10):949-61. doi: 10.4161/cbt.25941. Epub 2013 Aug 2.
10
The sensitivity of diffuse large B-cell lymphoma cell lines to histone deacetylase inhibitor-induced apoptosis is modulated by BCL-2 family protein activity.弥漫性大 B 细胞淋巴瘤细胞系对组蛋白去乙酰化酶抑制剂诱导凋亡的敏感性受 BCL-2 家族蛋白活性的调节。
PLoS One. 2013 May 7;8(5):e62822. doi: 10.1371/journal.pone.0062822. Print 2013.
引用本文的文献
1
Ionizing radiation-induced disruption of Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes causing spermatogenesis dysfunction.电离辐射导致初级精母细胞中Rela-Bclaf1-剪接体调节轴的破坏，从而引起精子发生功能障碍。
Cell Commun Signal. 2025 Jan 31;23(1):58. doi: 10.1186/s12964-025-02067-5.
2
LMK-235 suppresses osteoclastogenesis and promotes osteoblastogenesis by inhibiting HDAC4.LMK-235 通过抑制组蛋白去乙酰化酶 4 来抑制破骨细胞生成并促进成骨细胞生成。
Sci Rep. 2024 Aug 28;14(1):19973. doi: 10.1038/s41598-024-70814-8.
3
Integrated bulk and single-cell RNA sequencing identifies an aneuploidy-based gene signature to predict sensitivity of lung adenocarcinoma to traditional chemotherapy drugs and patients' prognosis.整合 bulk 和单细胞 RNA 测序，确定了基于非整倍体的基因特征，可预测肺腺癌对传统化疗药物的敏感性和患者的预后。
PeerJ. 2024 Jun 24;12:e17545. doi: 10.7717/peerj.17545. eCollection 2024.
4
Pan-Cancer Analysis Identifies BCLAF1 as a Potential Biomarker for Renal Cell Carcinoma.泛癌分析确定BCLAF1为肾细胞癌的潜在生物标志物。
Biochem Genet. 2025 Apr;63(2):1479-1508. doi: 10.1007/s10528-024-10773-x. Epub 2024 Apr 4.
5
BCLAF1 binds SPOP to stabilize PD-L1 and promotes the development and immune escape of hepatocellular carcinoma.BCLAF1 结合 SPOP 以稳定 PD-L1 并促进肝癌的发展和免疫逃逸。
Cell Mol Life Sci. 2024 Feb 10;81(1):82. doi: 10.1007/s00018-024-05144-z.
6
A Selective Histone Deacetylase Inhibitor Induces Autophagy and Cell Death via SCNN1A Downregulation in Glioblastoma Cells.一种选择性组蛋白去乙酰化酶抑制剂通过下调胶质母细胞瘤细胞中的SCNN1A诱导自噬和细胞死亡。
Cancers (Basel). 2022 Sep 19;14(18):4537. doi: 10.3390/cancers14184537.
7
Function of BCLAF1 in human disease.BCLAF1在人类疾病中的作用。
Oncol Lett. 2022 Feb;23(2):58. doi: 10.3892/ol.2021.13176. Epub 2021 Dec 22.
8
Bcl-2-associated transcription factor 1 Ser290 phosphorylation mediates DNA damage response and regulates radiosensitivity in gastric cancer.Bcl-2 相关转录因子 1 Ser290 磷酸化介导胃癌中的 DNA 损伤反应并调节放射敏感性。
J Transl Med. 2021 Aug 9;19(1):339. doi: 10.1186/s12967-021-03004-z.
9
BCLAF1 induces cisplatin resistance in lung cancer cells.BCLAF1诱导肺癌细胞产生顺铂耐药性。
Oncol Lett. 2020 Nov;20(5):227. doi: 10.3892/ol.2020.12090. Epub 2020 Sep 11.
10
Epigenetic Therapy as a Putative Molecular Target to Modulate B Cell Biology and Behavior in the Context of Immunological Disorders.表观遗传学治疗作为一种潜在的分子靶点，可调节免疫紊乱背景下 B 细胞的生物学和行为。
J Immunol Res. 2020 Feb 8;2020:1589191. doi: 10.1155/2020/1589191. eCollection 2020.
本文引用的文献
1
Chromosomal abnormality variation detected by G-banding is associated with prognosis of diffuse large B-cell lymphoma treated by R-CHOP-based therapy.G 带检测到的染色体异常变异与基于 R-CHOP 治疗的弥漫性大 B 细胞淋巴瘤的预后相关。
Cancer Med. 2018 Mar;7(3):655-664. doi: 10.1002/cam4.1342. Epub 2018 Feb 23.
2
Molecular heterogeneity in diffuse large B-cell lymphoma and its implications in clinical diagnosis and treatment.弥漫性大 B 细胞淋巴瘤的分子异质性及其在临床诊断和治疗中的意义。
Biochim Biophys Acta Rev Cancer. 2018 Apr;1869(2):85-96. doi: 10.1016/j.bbcan.2018.01.001. Epub 2018 Jan 11.
3
miR-194-5p/BCLAF1 deregulation in AML tumorigenesis.miR-194-5p/BCLAF1在急性髓系白血病肿瘤发生中的失调。
Leukemia. 2018 Feb;32(2):573. doi: 10.1038/leu.2017.310. Epub 2017 Dec 22.
4
A phase I/II trial of vorinostat (SAHA) in combination with rituximab-CHOP in patients with newly diagnosed advanced stage diffuse large B-cell lymphoma (DLBCL): SWOG S0806.一项评估伏立诺他（SAHA）联合利妥昔单抗-环磷酰胺、多柔比星、长春新碱、泼尼松（R-CHOP）方案治疗初治晚期弥漫大 B 细胞淋巴瘤（DLBCL）的 I/II 期临床研究：SWOG S0806 研究。
Am J Hematol. 2018 Aug;93(4):486-493. doi: 10.1002/ajh.25010. Epub 2018 Jan 25.
5
Diffuse large B-cell lymphoma.弥漫性大 B 细胞淋巴瘤。
Pathology. 2018 Jan;50(1):74-87. doi: 10.1016/j.pathol.2017.09.006. Epub 2017 Nov 20.
6
Silencing heme oxygenase-1 increases the sensitivity of ABC-DLBCL cells to histone deacetylase inhibitor and .沉默血红素加氧酶-1可增加ABC-DLBCL细胞对组蛋白脱乙酰酶抑制剂和的敏感性。
Oncotarget. 2017 Jul 28;8(45):78480-78495. doi: 10.18632/oncotarget.19652. eCollection 2017 Oct 3.
7
Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma.弥漫性大B细胞淋巴瘤的遗传和功能驱动因素
Cell. 2017 Oct 5;171(2):481-494.e15. doi: 10.1016/j.cell.2017.09.027.
8
Overexpression of heme oxygenase-1 in bone marrow stromal cells promotes microenvironment-mediated imatinib resistance in chronic myeloid leukemia.骨髓基质细胞中血红素加氧酶-1的过表达促进慢性髓性白血病中微环境介导的伊马替尼耐药。
Biomed Pharmacother. 2017 Jul;91:21-30. doi: 10.1016/j.biopha.2017.04.076. Epub 2017 Apr 23.
9
Beyond RCHOP: A Blueprint for Diffuse Large B Cell Lymphoma Research.超越RCHOP方案：弥漫性大B细胞淋巴瘤研究蓝图
J Natl Cancer Inst. 2016 Dec 16;108(12). doi: 10.1093/jnci/djw257. Print 2016 Dec.
10
Overexpression of heme oxygenase-1 induced by constitutively activated NF-κB as a potential therapeutic target for activated B-cell-like diffuse large B-cell lymphoma.NF-κB 持续激活诱导血红素加氧酶-1 过表达作为激活 B 细胞样弥漫大 B 细胞淋巴瘤的潜在治疗靶点。
Int J Oncol. 2016 Jul;49(1):253-64. doi: 10.3892/ijo.2016.3529. Epub 2016 May 17.
Zotero 插件