Research on the mechanism of HOPX-HDAC2 interaction inducing differentiation blockage in acute myeloid leukemia

IF 3.3 4区医学 Q2 HEMATOLOGY Hematological Oncology Pub Date : 2024-09-07 DOI:10.1002/hon.3307

Fang He, Yan Tu, Lihong Ni

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Abstract

Homeodomain-only protein homeobox (HOPX) mainly exerts its transcriptional repression by physically sequestering the serum co-repressor and recruiting histone deacetylase (HDAC), possessing important potential as a prognostic gene in acute myeloid leukemia (AML). HDACs play crucial roles in cell growth, gene regulation, and metabolism, and they are also important factors in promoting AML progression. Therefore, this project attempts to investigate whether HOPX affects AML progression by interacting with HDAC2 protein. Bioinformatics analysis was employed to identify potential prognostic genes in AML. Flow cytometry and MTT assays were performed to analyze the cellular biological functions of the AML prognostic marker HOPX. The interaction network of HOPX was analyzed using the Search Tool for the Retrieval of Interacting Genes database, and the interaction between HOPX and HDAC2 was observed using endogenous and exogenous immunoprecipitation. HOPX is highly expressed in AML cells. Further research uncovered that low expression of HOPX can repress the proliferation activity, anti-apoptotic ability, and differentiation blockage of AML cells. Moreover, mechanistically, HOPX induced AML differentiation blockage and malignant progression through interaction with HDAC. HOPX can serve as a prognostic marker for AML and can interact with HDAC2 to induce AML differentiation blockage and malignant progression.

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HOPX-HDAC2相互作用诱导急性髓性白血病分化阻断机制的研究

纯同源异构体蛋白（HOPX）主要通过与血清共抑制因子的物理隔离和招募组蛋白去乙酰化酶（HDAC）来发挥其转录抑制作用，具有作为急性髓性白血病（AML）预后基因的重要潜力。HDAC 在细胞生长、基因调控和新陈代谢中起着至关重要的作用，也是促进 AML 进展的重要因素。因此，本项目试图研究HOPX是否通过与HDAC2蛋白相互作用来影响AML的进展。本研究采用生物信息学分析来确定急性髓细胞性白血病的潜在预后基因。流式细胞术和MTT试验分析了AML预后标志物HOPX的细胞生物学功能。使用检索相互作用基因数据库的搜索工具分析了HOPX的相互作用网络，并使用内源和外源免疫沉淀技术观察了HOPX与HDAC2之间的相互作用。HOPX 在 AML 细胞中高表达。进一步研究发现，低表达的HOPX可抑制AML细胞的增殖活性、抗凋亡能力和分化阻滞。此外，从机理上讲，HOPX通过与HDAC相互作用，诱导AML分化受阻和恶性进展。HOPX可作为急性髓细胞性白血病的预后标志物，并可与HDAC2相互作用，诱导急性髓细胞性白血病分化受阻和恶性进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hematological Oncology 医学-血液学

CiteScore

4.20

自引率

6.10%

发文量

147

审稿时长

>12 weeks

期刊介绍： Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged: -Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders -Diagnostic investigations, including imaging and laboratory assays -Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases -Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies -Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems. Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.