Expression and Regulation Network of HDAC3 in Acute Myeloid Leukemia and the Implication for Targeted Therapy Based on Multidataset Data Mining.

Minhua Li,Yi Kong,Zesong Li,Danny Wu,Xiao Zhu,Xiaojie Chen,Jingyu Zhang,Xinming Li,Yueyuan Zhong,Wenqing Chen,Feifei Lan,Ning Li,Chen Li,Yue Yang,Yingqi Shao,Min Tang

doi:10.1155/2022/4703524

Abstract

Background Histone deacetylase 3 (HDAC3) plays an important role in the development and progression of a variety of cancers, but its regulatory mechanism in acute myeloid leukemia (LAML) is not entirely understood. Methods We analyzed the expression of HDAC3 in normal and cancerous tissues using Oncomine, UALCAN, and GEO databases. Changes of the HDAC3 gene were analyzed by cBioPortal. The genes coexpressed with HDAC3 were analyzed by WebGestalt, and the predicted signaling pathways in KEGG were discussed. Results We discovered that the expression of HDAC3 was elevated in some types of acute myeloid leukemia. The HDAC3 gene has a strong positive correlation with SLC25A5, NDUFA2, Cox4I1, and EIF3K, which regulate cell growth and development. HDAC3 transcription is higher in patients with FLT3 mutation than in healthy people. HDAC3 can be directly involved in regulating the thyroid hormone signaling pathway. MEF2D is directly involved in the cGMP-PKG signaling pathway, and the HDAC3 gene has a strong synergistic relationship with MEF2D. HDAC3 is indirectly involved in the cGMP-PKG signaling pathway, thereby indirectly regulating the expression levels of p53 and p21 genes in patients with LAML. Genomics of Drug Sensitivity in Cancer (GDSC) database analysis revealed that the application of the HDAC3 inhibitor can inhibit the proliferation of leukemia cells. Conclusions Therefore, our data suggest that HDAC3 may be a possible therapeutic target for acute myeloid leukemia.

Highlights

Acute myeloid leukemia (LAML) is a group of highly heterogeneous hematologic tumors caused by malignant clonal proliferation, dysdifferentiation, and blocked apoptosis of hematopoietic stem cells [1]
We first analyzed the deoxyribonucleic acid (DNA) copy number variation (CNV) and messenger RNA transcription levels of Histone deacetylase 3 (HDAC3) in acute myeloid leukemia using Oncomine database to investigate the expression of HDAC3 in acute myeloid leukemia
In the Andersson leukemia dataset, HDAC3 over expression was found in LAML compared with normal bone marrow with a fold change of 1.729 in acute myeloid leukemia (p < 0:05)

Summary

Introduction

Acute myeloid leukemia (LAML) is a group of highly heterogeneous hematologic tumors caused by malignant clonal proliferation, dysdifferentiation, and blocked apoptosis of hematopoietic stem cells [1]. Histone deacetylase 3 (HDAC3) plays an important role in the development and progression of a variety of cancers, but its regulatory mechanism in acute myeloid leukemia (LAML) is not entirely understood. The genes coexpressed with HDAC3 were analyzed by WebGestalt, and the predicted signaling pathways in KEGG were discussed. We discovered that the expression of HDAC3 was elevated in some types of acute myeloid leukemia. HDAC3 can be directly involved in regulating the thyroid hormone signaling pathway. MEF2D is directly involved in the cGMP-PKG signaling pathway, and the HDAC3 gene has a strong synergistic relationship with MEF2D. HDAC3 is indirectly involved in the cGMP-PKG signaling pathway, thereby indirectly regulating the expression levels of p53 and p21 genes in patients with LAML. Genomics of Drug Sensitivity in Cancer (GDSC) database analysis revealed that the application of the HDAC3 inhibitor can inhibit the proliferation of leukemia cells. Our data suggest that HDAC3 may be a possible therapeutic target for acute myeloid leukemia

Methods

Results

Discussion

Conclusion