Table 2 Role of aberrant lysine acylations in tumorigenesis
Acylation | Tumour type | Histone/protein involved | Description | Ref |
|---|---|---|---|---|
Kcr | Prostate cancer | / | Hypocrotonylation on histones induced by BRD4 inhibitors hampers the proliferation and migration of prostate cancer | [32] |
Colorectal cancer | H3K18;ENO1 | Intestinal microbiota depletion resultes in increased expression of HDAC2 to downregulate Kcr level and relates to tumorigenesis in colon cancer;K420cr of ENO1 facilitates the proliferation, migration and invasion of colorectal cancer | ||
Leukemia | / | Efficiently epigenetic impact of YEATS domain on leukemia may partially owing to its interaction with histone Kcr | ||
Liver cancer | / | Kcr expression correlates with TNM stage in liver cancer and increasing Kcr level leads to undermined cell migration and proliferation | [90] | |
Long cancer | CAV1; Complement C3 | CAV1 and Complement C3 as regulators of tumour metastasis or tumour microenvironment are significantly regulated with Kcr marks | [91] | |
Kla | Ocular melanoma | H3K18 | H3K18la promotes the expression of YTHDF2 and enhances the degradation of m6A modified PER1 and TP53 mRNAs thus driving oncogenesis | [99] |
Lung cancer | / | Lactate promotes cell proliferation and modulates cellular metabolism at least in part through histone lactylation-mediated gene expression in non-small cell lung cancer cells | [100] | |
Breast cancer | / | Regulated transcription of key oncogenes, tumour suppressors as well as cell cycle and proliferation genes may be partially ascribed to histone Kla on relevant gene promoters in breast cancer | [101] | |
AM | Human pancreatic ductal adenocarcinoma | H3K79; H3K122;PGAM1;GLS | H3K79succ promotes YWHAZ expression and represses β-catenin degradation to enhance cell proliferation, migration and invasion of PDAC; Ksucc of H3K122 and PGM1 mediated by HAT1 are required for pancreatic cancer growth; Ksucc of GLS facilitates its oligomerization and activity to promote tumour growth of PDAC | |
Liver cancer | H3K79;H3K122;PGAM1 | Ksucc of H3K79 plays a vital role in HBV infection and liver tumour progression; Ksucc of H3K122 and PGM1 mediated by HAT1 are required for liver cancer growth | ||
Glioblastoma | H3K79 | H3K79succ promotes gene expression and tumour growth in glioblastoma cells | [103] | |
Gastric cancer | S100A10;LDHA; CALD1;OGDH | Elevated Ksucc of S100A10 and LDHA hinders their degradation thus enhancing tumour invasion and migration; desuccinylation of OGDH dampens its activity and subsequently suppresses tumorigenesis in GC; K569succ of CALD1 significantly decreases in GC and may function as a promising biomarker | ||
Prostate cancer | LDHA | Ksucc of LDHA increases its activity in promoting prostate tumour metastasis | [53] | |
Lung cancer | SOD1;PKM2 | K123succ of SOD1 decreases its activity in antioxidation and anti-tumor effect in lung tumour cells; desuccinylation of PKM2 impedes its activity to eliminate reactive oxygen species(ROS) and boost tumour growth | ||
Colon cancer | PKM2;CS;SHMT2 | K433succ of PKM2 induced its mitochondrial translocation to promote cell survival and tumour development against nutritional depletion; desuccinylation of CS accelerates colon cancer growth; SIRT5-mediated desuccinylation of SHMT2 increases its activity to foster tumour progression; elevated Ksucc caused by DCA may help to realize DCA’s anti-tumor effect | ||
Renal cell carcinoma | SDHA | SDHA is desuccinylated and fosters tumour proliferation; Ksucc is intertwined with energy metabolism in RCC cells | ||
Breast cancer | GLS | Hypersuccinylation brings about the degradation of GLS and impedes glutamine consumption of tumour cells | ||
Esophageal squamous cell carcinoma | / | Ksucc is reduced in ESCC and restored Ksucc restricts cell growth, migration and invasion | [141] | |
Kpr | Leukemia | H3K23 | Hyperpropionylation in leukemia cell may corelate with hematopoiesis and leukemogenesis | [147] |
Glioma | / | Kpr induced by HDACi might become a monitor of HDACi’s pharmacological actions and interactions with malignant cells | [57] | |
Colon cancer | / | Kpr induced by propionate facilitates NKG2D ligand expression and holds promise for immune activating anticancer therapy | [60] | |
Kbu | Neuroblastoma | H2BK5, H4K12 | Kbu induced by SAHA reconstructs chromatin and reactivates gene expression to inhibit tumorigenesis | [56] |
Colorectal cancer | H2BK5, H3K18 and H3K23 | Kbu induced by largazole-7 may partially account for its antitumor effect | [161] | |
Ewing sarcoma | / | Kbu induced by NaB may take part in its inhibiting tumour growth effect | [162] | |
Esophageal squamous cell carcinoma | H3K18, H3K23, H3K79 and H4K77 | Abundant histone sites with Kbu have been found in ESCC and may associate with tumour growth | [163] | |
Kma | Colorectal cancer | SDHA;TPI | Demalonylation of SDHA and TPI impairs their activities and prompts the recurrence of CRC | |
Kglu | Colorectal cancer | GLUD1 | GLUD1 can be deglutaryled at K545 and activated to promote cellular glutaminolysis and colorectal carcinogenesis | [176] |
Khib | Liver cancer | H4K8;ENO1 | de-2-hydroxyisobutyrylation of H4K8 on HBV cccDNA minichromosome can restrict HBV transcription and replication in hepatoma cells; K281hib of ENO1 can be repressed by aspirin to cause proliferation defective of liver cancer cells | |
Bladder cancer | / | Khib-modified histones involve in HSP inhibitors-treated bladder cancer cells to inhibit tumour progression | [184] | |
Oral squamous cell carcinoma | / | The protein expression within the actin cytoskeleton regulatory pathway and their Khib modification levels significantly changes in oral squamous cell carcinoma, which may be important for tumour progression | [187] | |
Kbhb | Liver cancer | H3K9 | H3K9bhb participates in the promotion of HCC stemness and progression induced by MAT2 | [197] |
Multiple cancers | P53 | P53 is modified by kbhb at lysines120, 319, and 370 and attenuates its anti-tumor effect in tumour cells | [68] |