Lysine crotonylation in disease: mechanisms, biological functions and therapeutic targets

Ji, Yu; Liu, Shanshan; Zhang, Yiqiao; Min, Yiyang; Wei, Luyang; Guan, Chengjian; Yu, Huajing; Zhang, Zhongtao

doi:10.1186/s13072-025-00577-7

Epigenetics & Chromatin

Table 2 The roles of Kcr in diseases

From: Lysine crotonylation in disease: mechanisms, biological functions and therapeutic targets

Disease category	Diseases	Biological context	Kcr level	Biological impact	References
Neurological system disorders	Alzheimer’s disease	U251 cells, brain tissues from Alzheimer’s disease mice	↑H3K27cr	Inhibit endocytosis	[53, 55]
	Hypoxic-ischemic encephalopathy	Cerebral cortex and hippocampus tissues from Neonatal hypoxic–ischemic brain damage rats	↑Pan-Kcr, ↑H3K9cr	SB ameliorates HIE	[56, 57]
	Depression	SH-SY5Y cells, prelimbic cortex tissues from chronic social defeat stress mice	↓Pan-Kcr	CDYL-mediated histone Kcr aggravated stress-induced depression	[58]
	Neuropathic pain	The trigeminal ganglia tissues from Cx3cr1^GFP mice and complete freund adjuvant induced inflammatory pain mice	↑Pan-Kcr	Kcr induces macrophage activation and inflammatory	[59]
	Neurodevelopmental diseases	Human neural stem/ progenitor cells and P19 embryonal carcinoma cells	↓Pan-Kcr, ↑H3K9Cr	Activates bivalent promoters to stimulate gene expression in nspc	[64,65,66]
Dental disorders	Osteogenic differentiation of PDLSCs	Human periodontal ligament stem cells	↑Pan-Kcr	Treatment with sodium crotonate (NaCr) and silencing ACSS2 affected the activation of the PI3K-AKT signaling pathway	[67]
	Oral squamous cell carcinoma	CAL27 cells	↑HSP90AB1 Kcr	HSP90AB1 Kcr in hypoxic conditions may enhance the glycolysis regulation ability in oral squamous cell carcinoma	[68]
Respiratory system disorders	Chronic obstructive pulmonary disease	Human lung tissues	↓PanKcr	Kcr impacts chronic obstructive pulmonary disease	[70]
	Non-small cell lung cancer	PEM-resistant non-small cell lung cancer cells and H1299 cells	↓H3K18cr, ↓BEX2 K59cr	Reduce proliferation of PEMresistant non-small cell lung cancer cells	[12, 71]
Cardiovascular system disorders	Ischemic heart disease	Vascular smooth muscle cells from mice with cardiac I/R injury, volatile mycocytes from isoprenaline induced neonatal rats	↑IDH3a K199cr, ↑TPM1 K28/29cr	Preserve myocardial function	[72,73,74]
	Hypertrophic cardiomyopathy	Cardiomyocytes from Echs1 mutant mice and ECHS1-expressing/siechs1 neonatal rats	↑H3K18cr, ↑H2BK12cr,↑NAE1 K238cr	Kcr is involved in cardiac hypertrophy	[76, 77]
	Cardiac dysfunction and arrhythmia	Cardiomyocytes from SIRT1 cardiac specific knockout mice	↑SERCA2a K120cr	Kcr induces cardiac dysfunction	[78]
Digestive system disorders	Liver fibrosis	Liver tissues from CCl₄ induced liver fibrosis rats	↓Pan-Kcr, ↓H2BK12cr, ↓H3K18cr	Improve the hepatic structure and fibrotic progression	[72]
	Hepatocellular carcinoma	HepG2 cells, liver tissues from Acox2 knockout mice	↓Crot Kcr, ↓Scp2 Kcr, ↓Hsd17b4 Kcr	Regulate hepatic metabolic homeostasis	[83]
		Huh-7 cells, HepG2 cells, liver tissues from female balb/c nude mice	↑PanKcr, ↑LamininA K265/270cr	Promote liver cancer cell proliferation	[36]
		HepG2 cells and MHCC97 cells, liver tissues from mice with liver tumor	↑PanKcr, ↑SEPT2	Promote cell invasive capability	[84]
		implantation	K74cr
		Human hepatoma-derived cells	↑PanKcr	Inhibit the movement and proliferation of hepatoma cells	[85]
	Colorectal cancer	HCT-116 cells, DLD-1 cells, LoVo cells and SW480 cells	↓H3K27cr	The level of H3K27cr was reduced during DNA damage in colon cancer	[42, 88, 89]
		Human colorectal cancer tissues	↑ENO1 K420cr	ENO1 K420cr promotes growth, migration, and invasion of CRC cells	[90]
		Human PBMCs	↑H2BK12cr	H2BK12cr may serve as a biomarker	[92]
	Pancreatic cancer	PANC-1 cells	↓MTHFD1 K354/553cr	MTHFD1 Kcr inhibited the development of pancreatic cancer by increasing resistance to ferroptosis	[18]
Urogenital system disorders	Acute kidney injury	Proximal tubular cells from folic acid induced mice	↑PanKcr	Against inflammation and mitochondrial stress	[52]
	Renal fibrosis	Human distal tubular cells and tubular epithelial cells	↓PanKcr, ↑H3K9cr	Alleviate IL-1β-dependent macrophage activation and tubular cell senescence, and delay renal fibrosis	[49, 95]
	Autosomal dominant polycystic kidney disease	WT 9–12 cells, kidney tissues from CDYL transgenic mice and Pkd1 knockout mice	↑Pan-Kcr, ↑H3K18cr	Overexpression of CDYL reduces Kcr and slows cyst growth	[98, 99]
	Prostate cancer	Human prostate cancer cell lines ( PC-3 cells, LNCaP cells, and C42B cells), human prostate cancer tissues	↓H3K18cr	Promote the function of Prostate cancer cells	[101]
Reproductive system disorders	Polycystic ovary syndrome	Ovarian tissues from mice	↑LONP1 K390cr	Kcr leads to mitochondrial dysfunction and oxidative stress	[102]
	Spermatogenesis disorder	Germ cells from mice	/	Regulate escape gene activation from inactive sex chromosomes in post-meiotic spermatids	[14]
		Spermatogenic cells from mice	↑PanKcr	Specifically mark testis specific genes	[9]
		Round spermatid tissues from CDYL transgenic mice	↓PanKcr, ↓H2BK12cr	CDYL-regulated histone Kcr regulates spermatogenesis and male fertility	[15]
	Cervical cancer	Human cervical cancer cells and the normal cervical epithelial cells	↑Pan-Kcr	Enhance cell proliferation, invasion, and migration of hela cells	[107]
Infectious disorders	AIDS	Human HIV latency cells	↑H3K4cr	Viral reactivation	[110]
		Human jurkat cells of HIV latency	↑PanKcr	Viral reactivation	[113]
	Bacterial infection	Porcine alveolar macrophages after T. Gondii infection from mice	↓H2BK12cr	Activation of immune response	[36, 115]
Metabolic disorders	Type 2 diabetes mellitus	HK-2 cells, kidney tissues from diabetic (db/db) mice	↑H3K27cr	Glucose uptake	[116, 117]
	Obesity	White adipocyte tissues from B3-adrenergic receptor (CL316,243) agonist induced the white fat browning mice	↑PanKcr	Modulation of white fat browning	[125, 126]

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ISSN: 1756-8935

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