The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Nucleophosmin acetylation and construction and expression of its modified sites mutants in breast cancer / 解剖学报

Objective To determine the acetylation level of nucleophosmin(NPM)in female breast cancer and to discuss its function through mutation of modified lysine sites.To construct positive and negative NPM mutants on its acetylated lysine sites and to express them in breast cancer cells.Methods Acetylation level and acetylated lysine sites of NPM in three breast cancer tissues and para-carcinoma tissues were detected by acetylome technology;NPM mutants were constructed by site-directed mutagenesis PCR,specific PCR products were digested by DpnI and transformed into Escherichia coli(E.coli)to obtain specific plasmids for mutants;The accuracy of mutants were verified by double restriction enzyme digestion and sequencing;The mutants were expressed in BT-549 cells by transient transfection and verified by RT-PCR method.Protein expression and acetylation level of NPM were validated by Western blotting;Function of NPM acetylation was analyzed by proteomic detection and bioinformatic analysis.Results The 27th and 32nd lysine of NPM were highly acetylated in breast cancer tissues,which were 2.76 and 2.22 times higher than those in adjacent normal tissues,respectively;The NPM mutants showed the same molecular weight as that of wild type NPM and contained expected mutation sites;Corresponding NPM mRNA levels of BT-549 cells transfected with NPM mutants were significantly increased.With the increase of wild type NPM expression level,NPM acetylation level increased,while decreased after 27th lysine underwent negative mutation.NPM acetylation can significantly change the expression levels of 101 proteins in BT-549 cells,which are enriched in regulation of cellular macromolecule biosynthesis,DNA-template transcription,RNA biosynthesis and RNA metabolism process.Conclusion NPM is highly acetylated in breast cancer and can play a key role in cellular macromolecule biosynthesis,DNA-templated transcription,RNA biosynthesis and RNA metabolism process.

Regulation of Histone Acetylation by Traditional Chinese Medicine in Prevention and Treatment of Alzheimer's Disease： A Review / 中国实验方剂学杂志

Alzheimer's disease （AD） is a neurodegenerative disease with progressive losses of memory and cognitive function as the main clinical manifestations. It is difficult to be cured because of the complex pathogenesis. Histone acetylation regulates gene transcription and chromosome structure remodeling without changing the coding sequences of genes， participating in the pathological process of AD via modulating the amyloid beta-protein （Aβ） deposition， Tau phosphorylation， neuron growth， and synaptic plasticity. Traditional Chinese medicine can prevent and control AS via multiple targets and pathways from a holistic view. Animal and cell experiments have proven that traditional Chinese medicine can attenuate AD by regulating histone acetylation. Focusing on the key role of histone acetylation in AD， this study reviews the relevant studies in the last five years from the aspects of active ingredients of traditional Chinese medicine and traditional Chinese medicine compound prescriptions. The available studies suggest that the main mechanisms involve antagonizing apoptosis， inhibiting oxidative stress， ameliorating Tau and Aβ deposition， maintaining synaptic function， nourishing neurons， and repairing myelin sheath. The treatment methods include invigorating kidney and tranquilizing mind， tonifying spleen and harmonizing middle energizer， and opening orifices and resolving phlegm. The commonly used herbal medicines in compound prescriptions include Poria， Glycyrrhizae Radix et Rhizoma， Chuanxiong Rhizoma， Acori Tatarinowii Rhizoma， and Paeoniae Radix Alba. The findings indicate that traditional Chinese medicine demonstrates great potential in the prevention and treatment of AD， providing a theoretical basis for the clinical treatment and research of AD.

Research progress on histone acetylation/methylation in oral diseases / 口腔疾病防治

@#Histone acetylation and methylation can affect chromatin conformation and regulate a variety of biological activities. Abnormal histone acetylation and methylation modifications are related to the occurrence and development of a variety of oral diseases. Histone acetylation and methylation increase or decrease in an orderly manner to regulate the development of teeth. Fluoride ions can destroy the balance between histone acetylation and methylation, which may be related to the occurrence of dental fluorosis. In addition, histone acetylation and methylation are involved in the regulation of oral inflammatory diseases. In the inflammatory microenvironment, the expression of histone acetyltransferase GCN5 decreases, and the expression of Dickkopf 1 (DKK1) decreases, activating the Wnt/β-catenin pathway and ultimately inhibiting the osteogenic differentiation of periodontal ligament stem cells. Enhancer of zeste homolog 2 (EZH2) and H3K27me3 levels were decreased in inflamed dental pulp tissues and cells. EZH2 inhibition inhibited the expression of interleukin (IL)-1b, IL-6 and IL-8 in human dental pulp cells under inflammatory stimulation. Histone acetylation/methylation modifications can interact with multiple signaling pathways to promote the occurrence and development of oral tumors and are related to the high invasiveness of salivary gland tumors. Small molecule drugs targeting histone acetylation and methylation-related enzymes can regulate the level of histone methylation/acetylation and have shown potential in the treatment of oral and maxillofacial diseases. For example, the histone deacetylase inhibitor vorinostat can inhibit the secretion of inflammation-related cytokines; it also promotes the maturation of odontoblasts and the formation of dentin-related matrix, demonstrating its potential in pulp preservation. Understanding the role of histone acetylation/methylation modifications in the occurrence and development of oral diseases will help promote research on epigenetic modifications in oral diseases and provide new perspectives for disease diagnosis and treatment.

Emodin regulates histone acetylation to promote pyroptosis and apoptosis of HpG2 hepatoma cells / 天津医药

Objective To study whether emodin,a natural product,can affect the level of histone acetylation in HpG2 hepatocellular carcinoma cells(HCC),and then accelerate the occurrence of pyroptosis and apoptosis in hepatocellular carcinoma cells,so as to provide a new target for the treatment of liver cancer.Methods CCK-8 method was used to detect the effect of different concentrations of emodin on the viability of HpG2 cells.Bioinformatics was used to analyze histone acetylation-related genes in patients with liver cancer in TCGA database.The correlation between the candidate gene lysine acetyltransferase 2A(KAT2A)and the apoptosis pathway was verified.qPCR method was used to detect the mRNA level of KAT2A in HepG2 cells and L02 cells.The effects of emodin on histone acetyltransferase(HAT)and histone deacetyltransferase(HDAC),interleukin 1β(IL-1β)and interleukin 18(IL-18)in HpG2 cells were detected by ELISA.The effect of emodin on the apoptosis of liver cancer cells was detected by flow cytometry.The expression level of cell apoptosis,pyroptosis-associated protein B lymphocytoma-2(Bcl-2),Bcl-2-related X protein(Bax),NOD-like receptor thermal protein domain-related protein 3(NLRP3),Caspase-1,Gasdermin family member DN terminal(GSDMD-N)and KAT2A were detected by Western blot assay.Results Emodin could reduce the activity of HpG2 cells,and the confidence interval of IC5095%was 58.12-66.52μmol/L.Compared with normal liver tissue,the expression of histone acetylation related gene mRNA was increased in HCC tissue,and the change of KAT2A was the highest[log2(Fold Change)=2.010,P＜0.01].In HCC tissue,the expression of KAT2A mRNA was negatively correlated with apoptosis pathway(rs=-0.230,P＜0.01).Compared with L02 cells,the expression of KAT2A mRNA in HepG2 was higher(P＜0.05).Compared with the control group,expression levels of HAT and HDAC decreased in the 60μmol/L emodin intervention group,expression levels of IL-18 and IL-1β increased,the apoptosis rate increased,expression levels of KAT2A and BAX decreased,and expression levels of Bcl-2,NLRP3,GSDMD-N and Caspase-1 increased(P＜0.05).Conclusion Emodin could inhibit the viability of hepatoma cells,accelerate apoptosis and pyroptosis,and its mechanism may be related to the regulation of KAT2A expression.

Abnormal modification of alpha-synuclein and its mechanism in Parkinson's disease / 中国组织工程研究

BACKGROUND:The formation of Lewy bodies due to abnormal α-synuclein aggregation is a characteristic pathological change in Parkinson's disease.In recent years,several studies have revealed that the formation of α-synuclein aggregates is closely related to its post-translational modifications.The modification of α-synuclein such as phosphorylation,nitration,acetylation,and ubiquitination has attracted extensive attention in the pathogenesis and progression of Parkinson's disease. OBJECTIVE:To review the research progress in the effect of modification types and sites of α-synuclein on the characteristic pathological formation and progression of Parkinson's disease. METHODS:PubMed and CNKI databases were searched by the first author with the key words of"α-synuclein,Parkinson's disease,phosphorylation,acetylation,ubiquitination,nitration"in English and Chinese respectively to collect and sort out the literature related to abnormal modification of α-synuclein in recent years.Finally,61 articles were included for further review. RESULTS AND CONCLUSION:Abnormal modification of α-synuclein is closely related to its protein structure and its positive and negative charges.Its amino terminus is positively charged and prone to ubiquitination and acetylation modifications.The central hydrophobic region is prone to forming β-pleated sheet due to its hydrophobic property.The carboxyl terminus is negatively charged,which is the main phosphorylation modification region.Phosphorylation modification sites promote phosphorylation modification and are closely related to α-synuclein aggregation,while protein kinases can target the activation of translational modifications,which may help to promote or inhibit aggregate formation.The degradation pathway of α-synuclein mainly plays a role in removing pathological proteins.Various kinase catalysts contribute to impaired protein ubiquitination modifications that lead to abnormal protein accumulation,thereby exacerbating neurodegeneration.The amino-terminal acetylation of α-synuclein improves the shuttle ability of the protein to the cell membrane and slows down the protein aggregation,which may be the protection target of nerve cells.However,the acetylation modification of the mutant protein produces the opposite effect.The protein nitration modification is mainly related to oxidative stress.The aggregation tendency of the protein modified by nitration is enhanced under the action of reactive oxygen species.Different post-translational modifications have different effects.Therefore,elucidating the main mechanisms of their post-translational modifications and inhibiting the post-translational modifications that contribute to protein aggregation may provide a reference for new targets for early diagnosis and treatment of Parkinson's disease.

Histone Acetylation Inhibits the Expression of Asthma Susceptibility Gene ADRB2 / 医学研究杂志

Objective To study the effect of acetylation modification regulated by histone deacetylase inhibitors(HDACi)and his-tone acetyltransferase(HAT)on β2-adrenergic receptor(ADRB2)gene.Methods ADRB2 promoter plasmid(pADRB2-1918)was transfected into BEAS-2B cells,and sodium butyrate(SoB)and trichostatin A(TSA)were added respectively.Adenovirus E1 A-relat-ed kDa protein(p300)plasmid and PADRB2-1918 plasmid were co-transfected into BEAS-2B cells to acetylate histone in BEAS-2B cells.The activity of ADRB2 promoter in BEAS-2B cells treated with SoB,TSA,and p300 was detected by dual-luciferase gene re-porter assay.SoB and TSA were added to BEAS-2B cells,or p300 plasmid was transfected into BEAS-2B cells to acetylate histone in BEAS-2B cells.The relative expression of ADRB2mRNA in BEAS-2B cells was detected by quantitative real-time PCR(qRT-PCR),and the expression of ADRB2 protein in BEAS-2B cells was detected by Western blot.Results SoB,TSA,and p300 plasmid were added into BEAS-2B cells,respectively,which participated in histone acetylation in BEAS-2B cells.We found that the activities of ADRB2 promoter,mRNA,and protein expressions in BEAS-2B cells were lower than those in the control group(P＜0.05),and the differences were statistically significant.Conclusion Histone acetylation can inhibit the expression of ADRB2 in asthma susceptible genes.

Research progress in histone acetylation in radiation-related DNA damage / 中华放射肿瘤学杂志

Radiotherapy is a first-line treatment for a variety of malignant tumors by inducing DNA damage to kill tumor cells. However, tumor cells have different sensitivities to radiotherapy, ultimately leading to different therapeutic effects. Histone acetylation, regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC), is involved in the regulation of cell radiation sensitivity by influencing DNA damage repair. The main mechanisms are recruiting DNA repair related proteins and mediating chromatin dynamic changes. In this article, the role of histone acetylation modification in tumor radiotherapy was reviewed, aming to provide the basis for the radiotherapy sensitization strategy based on histone acetylation.

Hedgehog pathway orchestrates the interplay of histone modifications and tailors combination epigenetic therapies in breast cancer

Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local interplay between different histone marks, leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment. However, in human cancers with diverse oncogenic activation, how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood. We herein discover that the hedgehog (Hh) pathway reprograms the histone methylation landscape in breast cancer, especially in triple-negative breast cancer (TNBC). This facilitates the histone acetylation caused by histone deacetylase (HDAC) inhibitors and gives rise to new therapeutic vulnerability of combination therapies. Specifically, overexpression of zinc finger protein of the cerebellum 1 (ZIC1) in breast cancer promotes Hh activation, facilitating the switch of H3K27 methylation (H3K27me) to acetylation (H3K27ac). The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes. Using multiple in vivo breast cancer models including patient-derived TNBC xenograft, we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer. Together, this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC.

Recent advance in role of adenovirus E1A binding protein p300 in glioblastoma / 中华神经医学杂志

Glioblastoma (GBM), characterized by rapid progression, easy recurrence and treatment resistance, is the most aggressive and lethal tumor of the central nervous system. Adenovirus E1A binding protein p300 (p300) serves rich functions as transcriptional coactivator and lysine acetyltransferase. Studies have shown that p300 plays an important role in the occurrence, proliferation, invasion and resistance to chemoradiotherapy of GBM. This paper reviews the structure and function of p300, and systematically expounds its various ways participating in GBM development and its translational perspectives, so as to provide references for GBM study.

Gestational dexamethasone exposure impacts hippocampal excitatory synaptic transmission and learning and memory function with transgenerational effects

The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons. Here we explored how gestational exposure to dexamethasone, a synthetic glucocorticoid commonly used in clinical practice, has lasting effects on offspring's learning and memory. Adult offspring rats of prenatal dexamethasone exposure (PDE) displayed significant impairments in novelty recognition and spatial learning memory, with some phenotypes maintained transgenerationally. PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations, and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory, but these changes failed to carry over to offspring of F5 and F7 generations. Mechanistically, altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission, which might be related to oocyte-specific high expression and transmission of miR-133a-3p. Together, PDE affects hippocampal excitatory synaptic transmission, with lasting consequences across generations, and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.

Protein phosphorylation involved in psychedelic-induced head-twitch response in rats / 中国药理学通报

Aim To investigate the potential protein post-translational modifications of psychedelic-induced Head-twith response and underling mechanism. Methods Psychedelics LSD, DOM, or Psilocin was administered to rats by intraperitoneal injection to induce head-twitch response, then the most effective dosage was identified to create animal models of head-twitch behavior. Western blot was performed in detecting the protein phosphorylation, acetylation, and ubiquitination in prefrontal cortex of SD rats after 10 min or 30 min injection. Results LSD (0.025 mg • kg~, i. p.), DOM (3 mg•kg

Role of epigenetic regulation of biological clock genes in tumors / 中国药理学通报

The circadian clock is regulated at the molecular level by transcriptional-translational feedback loop of clock genes, which ensures that a variety of physiological processes have a-round 24 h circadian rhythms, including cell metabolism, cell proliferation, cell apoptosis and tumorigenesis, to maintain the homeostasis. Thus, the disturbance of circadian clock will disrupt homeostasis, causing various diseases, including neoplasm, metabolic syndrome, Parkinson's disease, COPD and cardiovascular diseases. Disturbance of circadian clock is closely related with tumorigenesis, and acts on various molecules and pathways leading to tumorigenesis, including oncogene and tumor suppressor gene, cell cycle, metabolic reprogramming, immune escape, endocrine disruption, alteration of gastrointestinal microbiome. This review focuses on changes in clock genes expression which disrupt cell cycle and may play a role in tumorigenesis, and epi-geneties, an important way to regulate gene expression, which can alter clock gene expression, thus playing an important role in the process of " the alternation of clock gene expression-disruption of cell cycle-tumorigenesis".

Regulation mechanism of post-translational modification of farnesoid X receptor / 中国临床药理学与治疗学

Farnesoid X receptor (FXR) is a nuclear receptor activated by bile acid that is involved in regulating gene expression related to bile acid, fat, glucose, and amino acid metabolism. The activity of FXR is regulated by a variety of post-translational modifications. Common post-translational modifications of FXR include O-GlcNAcylation, phosphorylation, acetylation, sumoylation, methylation, etc. These post-translational modifications may affect FXR binding of DNA and ligand, heterodimerization, and subcellular localization, and may specifically regulate downstream gene transcription and expression. Different post-translational modifications can lead to changes in FXR stability and biological function, which are closely related to the occurrence of diseases. This paper aims to review the post-translational modification of FXR in the past five years and the mechanisms involved in disease regulation, to explore the effects of post-translational modification on the physiological function of FXR and to provide a theoretical basis for mechanism research targeting FXR.

Research progress in epigenetic pharmacological effects of rhein / 中国中药杂志

Rhein, which is one of the main active components of Rheum palmatum, has a range of pharmacological activities such as the regulation of the metabolism of glucose and lipids, anti-inflammatory, anti-tumor, anti-fibrosis, etc. Epigenetics refers to the heritable variation of gene expression without altering the DNA sequence. It is involved in the emergence and development of inflammation, renal fibrosis, diabetes, cancer, atherosclerosis, and other diseases, thus becoming a new strategy for the treatment of many di-seases. A series of studies have shown that epigenetic modification may be a common molecular mechanism of various pharmacological effects of rhein. This paper summarized the effects of rhein on the regulation of epigenetic modification and its underlying mechanisms, which involve the regulation of DNA methylation, protein acetylation, and RNA methylation, so as to provide a basis for the development and application of rhein.

Histone deacetylase inhibitor pracinostat suppresses colorectal cancer by inducing CDK5-Drp1 signaling-mediated peripheral mitofission / 药物分析学报

Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofission-associated cell death(MFAD)by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy.By screening a series of pan-inhibitors,we identified pracinostat,a pan-histone deacetylase(HDAC)inhibitor,as a novel MFAD inducer,that exhibited a significant anticancer effect on colorectal cancer(CRC)in vivo and in vitro.Pracinostat increased the expression of cyclin-dependent kinase 5(CDK5)and induced its acetylation at residue lysine 33,accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynamin-related protein 1(Drp1)-mediated mitochondrial peripheral fission.CRC cells with high level of CDK5(CDK5-high)displayed midzone mitochondrial division that was associated with oncogenic phenotype,but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells.Mechanistically,pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor(MFF)to mitochondrial fission 1 protein(FIS1).Thus,our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells,which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.

SIRT1 activation synergizes with FXR agonism in hepatoprotection via governing nucleocytoplasmic shuttling and degradation of FXR

Farnesoid X receptor (FXR) is widely accepted as a promising target for various liver diseases; however, panels of ligands in drug development show limited clinical benefits, without a clear mechanism. Here, we reveal that acetylation initiates and orchestrates FXR nucleocytoplasmic shuttling and then enhances degradation by the cytosolic E3 ligase CHIP under conditions of liver injury, which represents the major culprit that limits the clinical benefits of FXR agonists against liver diseases. Upon inflammatory and apoptotic stimulation, enhanced FXR acetylation at K217, closed to the nuclear location signal, blocks its recognition by importin KPNA3, thereby preventing its nuclear import. Concomitantly, reduced phosphorylation at T442 within the nuclear export signals promotes its recognition by exportin CRM1, and thereby facilitating FXR export to the cytosol. Acetylation governs nucleocytoplasmic shuttling of FXR, resulting in enhanced cytosolic retention of FXR that is amenable to degradation by CHIP. SIRT1 activators reduce FXR acetylation and prevent its cytosolic degradation. More importantly, SIRT1 activators synergize with FXR agonists in combating acute and chronic liver injuries. In conclusion, these findings innovate a promising strategy to develop therapeutics against liver diseases by combining SIRT1 activators and FXR agonists.

Knockdown of ACC1 promotes migration of esophageal cancer cell / 中华肿瘤杂志

Objective: To investigate the effect of acetyl-CoA carboxylase 1 (ACC1) knockdown on the migration of esophageal squamous cell carcinoma (ESCC) KYSE-450 cell and underlying mechanism. Methods: Lentiviral transfection was conducted to establish sh-NC control cell and ACC1 knocking down cell (sh-ACC1). Human siRNA HSP27 and control were transfected by Lipo2000 to get si-HSP27 and si-NC. The selective acetyltransferase P300/CBP inhibitor C646 was used to inhibit histone acetylation and DMSO was used as vehicle control. Transwell assay was performed to detect cell migration. The expression of HSP27 mRNA was examined by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and the expressions of ACC1, H3K9ac, HSP27 and epithelial-mesenchymal transition-related proteins E-cadherin and Vimentin were detected by western blot. Results: The expression level of ACC1 in sh-NC group was higher than that in sh-ACC1 group (P<0.01). The number of cell migration in sh-NC group was (159.00±24.38), lower than (361.80±26.81) in sh-ACC1 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC group were statistically significant compared with sh-AAC1 group (P<0.05). The migrated cell number in sh-NC+ si-NC group was (189.20±16.02), lower than (371.60±38.40) in sh-ACC1+ si-NC group (P<0.01). The migrated cell number in sh-NC+ si-NC group was higher than that in sh-NC+ si-HSP27 group (152.40±24.30, P<0.01), and the migrated cell number in sh-ACC1+ si-NC group was higher than that in sh-ACC1+ si-HSP27 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC+ si-NC group were significantly different from those in sh-ACC1+ si-NC and sh-NC+ si-HSP27 groups (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-ACC1+ si-NC group were significantly different from those in sh-ACC1+ si-HSP27 group (P<0.01). After 24 h treatment with C646 at 20 μmmo/L, the migrated cell number in sh-NC+ DMSO group was (190.80±11.95), lower than (395.80±17.10) in sh-ACC1+ DMSO group (P<0.01). The migrated cell number in sh-NC+ DMSO group was lower than that in sh-NC+ C646 group (256.20±23.32, P<0.01). The migrated cell number in sh-ACC1+ DMSO group was higher than that in sh-ACC1+ C646 group (87.80±11.23, P<0.01). The protein expressions of H3K9ac, HSP27, E-cadherin and Vimentin in sh-NC+ DMSO group were significantly different from those in sh-ACC1+ DMSO group and sh-NC+ C646 group (P<0.01). The protein expression levels of H3K9ac, HSP27, E-cadherin and Vimentin in sh-ACC1+ DMSO group were significantly different from those in sh-ACC1+ C646 group (P<0.01). Conclusion: Knockdown of ACC1 promotes the migration of KYSE-450 cell by up-regulating HSP27 and increasing histone acetylation.

Sevoflurane inhibits proliferation and invasion of breast cancer cells by promoting SIRT2 expression and inducing ACLY deacetylation / 中华内分泌外科杂志

Objective:To explore the effects of sevoflurane (Sev) on proliferation and invasion of breast cancer cells.Methods:Normal human breast epithelial cell line MCF10A and human breast cancer cell line MCF7 were purchased. The expression level of sirtuin 2 (SIRT2) , ATP citrate lyase (ACLY) in breast cancer cells and acetylation level of ACLY were measured. Breast cancer cells were divided into the following groups: Control group, 2% SEV group, 4% SEV group, si-NC group, si-SIRT2 group, 4% SEV+si-NC group, 4% SEV+si-SIRT2 group, SIRT2 group, SIRT2+ACLY-WT group, SIRT2+ACLY-3KQ group, SIRT2+ACLY-3KQ+4% SEV group, si-ACLY group, si-ACLY+ACLY-WT group, si-ACLY+ACLY-3KQ group. MTT and Transwell assay were used to detect cell proliferation and invasion.Results:Compared with MCF-10A cells (1.00±0.15) , SIRT2 was low expressed in Control group cells (0.43±0.03) ( q=11.98, P<0.001) , SEV could induce the expression of SIRT2 ( F=88.71, P<0.001) . In addition, ACLY and ACLY-3K acetylation level were up-regulated in breast cancer cells (all P<0.05) . Knockdown of SIRT2 or overexpression of ACLY and ACLY-3KQ could promote the proliferation and invasion of MCF7 cells (all P<0.05) , while SEV, overexpression of SIRT2 or knockdown of ACLY showed the opposite effects (all P<0.05) . Conclusion:Sev may inhibit the proliferation and invasion of breast cancer cells through SIRT2, which may be related to the regulation of ACLY deacetylation.

Research progress of histone acetylation in prevention and treatment of heart failure and new ideas based on traditional Chinese medicine / 中国中药杂志

Chronic heart failure(CHF) has become a worldwide public health problem due to its high morbidity and mortality, which seriously endangers people's lifespan and quality of life. In recent years, the treatment strategy of CHF has shifted its emphasis on short-term improvement and transformation of hemodynamics to long-term repair as well as improvement of the biological properties of heart failure. At present, with the continuous deepening of medical research, it has been found that histone acetylation is closely related to the occurrence and development of CHF. Traditional Chinese medicine, via regulating histone acetylation, delays ventricular remodeling, improves energy metabolism, inhibits fibrosis and cardiomyocyte hypertrophy, and intervenes in the development process of heart failure, thus reducing the mortality and the readmission rate and ultimately improving long-term prognosis. Therefore, this study reviewed the mechanism of histone acetylation in the treatment of heart failure as well as its prevention and treatment with traditional Chinese medicine, to provide reference for clinical treatment of CHF.