Histone deacetylase 10, a potential epigenetic target for therapy

Abstract

Histone deacetylase (HDAC) 10, a class Ⅱ family, has been implicated in various tumors and non-tumor diseases, which makes the discovery of biological functions and novel inhibitors a fundamental endeavor. In cancers, HDAC10 plays crucial roles in regulating various cellular processes through its epigenetic functions or targeting some decisive molecular or signaling pathways. It also has potential clinical utility for targeting tumors and non-tumor diseases, such as renal cell carcinoma, prostate cancer, immunoglobulin A nephropathy, intracerebral hemorrhage, human immunodeficiency virus (HIV) infection and schizophrenia. To data, relatively few studies have investigated HDAC10-specific inhibitors. Therefore, it is important to study the biological functions of HDAC10 for the future development of specific HDAC10 inhibitors. In this review, we analyzed the biological functions, mechanisms, and inhibitors of HDAC10, which makes HDAC10 an appealing therapeutic target.

Histone deacetylase-10 liberates spermidine to support polyamine homeostasis and tumor cell growth

“…These data suggest the importance of subcellular HDAC10 localization, which hints at the catalytic mechanism of action based on substrate availability, as N 8 -AcSpd deacetylation occurs in the cytoplasm. Conversely, nuclear localization of HDAC10 may be associated with its potential histone deacetylase activity (1,10).…”

“…Nuclear N 8 -acetylation of spermidine (Spd) is believed to facilitate its transport to the cytoplasm, where HDAC10 mediates its deacetylation back to spermidine ( 1 , 3 , 4 , 5 ). HDAC10 has been shown to have roles in autophagy, differentiation, DNA repair, exocytosis, and chemoresistance ( 6 , 7 , 8 , 9 ), as well as epigenetic regulation ( 10 ). However, none of these roles have been clearly linked to its function as a polyamine deacetylase.…”

Emerging Role of HDACs in Regeneration and Ageing in the Peripheral Nervous System: Repair Schwann Cells as Pivotal Targets

“…HDAC6 and HDAC10 are expressed in the brain, heart, liver, kidney, pancreas, and spleen [ 10 , 24 ].…”

Targeting lactate metabolism and glycolytic pathways in the tumor microenvironment by natural products: A promising strategy in combating cancer

“…23 Histone deacetylases (HDACs) are a large family of enzymes that are known to be key regulators in acetylation of nuclear histones and exhibit major functions in the onset and progression of cancer. 49 AMPK affects HDAC10 and increases gene transcription of the glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme in the pentose phosphate pathway, ultimately promotes cancer progression. 23 Myeloid-derived suppressor cells (MDSCs) induce immunosuppressive responses in the tumor microenvironment and allow cancer cells to escape from immune system, resulting tumor growth.…”

“…AMPK promotes the glycolysis pathway by increasing glucose uptake via GLUT1 and PFK‐1 upregulation, resulting in the Warburg effect and lactate production 23 . Histone deacetylases (HDACs) are a large family of enzymes that are known to be key regulators in acetylation of nuclear histones and exhibit major functions in the onset and progression of cancer 49 . AMPK affects HDAC10 and increases gene transcription of the glucose‐6‐phosphate dehydrogenase (G6PD), a rate‐limiting enzyme in the pentose phosphate pathway, ultimately promotes cancer progression 23 .…”