Histone deacetylase 3 (HDAC3) inhibits breast cancer cell pyroptosisby via regulating miR-625/ASF1B axis / 中华内分泌外科杂志

Objective:To investigate the effects of histone deacetylase 3 (HDAC3) on the pyroptosis of breast cancer (BC) cells via regulating miR-625/anti-silencing function 1B (ASF1B) and its mechanism.Methods:The expression level of HDAC3, miR-625 and ASF1B in BC tissue, adjacent normal tissue, BC cell lines (T47D, MCF7 and MDA-MB-231) and human normal breast epithelial cell MCF-10A was detected by qRT-PCR. The expression level of cell pyroptosis related protein NLRP3, Caspase-1 and GSDMD was detected by Western blot. The expression level of IL-18 and IL-1βwere detected by ELISA. ChIP experiment was used to determine the interaction between HDAC3 and miR-625. The dual luciferase reporter assay was used to verifiy the targeted regulation between miR-625 and ASF1B.Results:Compared with adjacent normal tissue and MCF-10A cells, the expression of HDAC3 and ASF1B was increased and the expression of miR-625 was decreased in BC tissue and cells (all P<0.05) . Compared with si-NC group, the protein expression level of NLRP3, Caspase-1 and GSDMD in si-HDAC3 group was increased, and the concentration of IL-18 and IL-1β in cell culture supernatant was increased (all P<0.05) . HDAC3 inhibited the expression of miR-625 by binding to the promoter region of miR-625 ( P<0.05) . Compared with si-HDAC3+miR-NC group, The expression of NLRP3, Caspase-1, GSDMD, IL-18 and IL-1β in si-HDAC3+miR-625 inhibitor group was decreased (all P<0.05) . ASF1B was confirmed as a target gene of miR-625, the level of pyroptosis related factors in si-HDAC3+pcDNA3.1-ASF1B group was significantly lower than that in si-HDAC3 + pcDNA3.1-NC group. Conclusion:HDAC3 up regulates the expression of ASF1B by inhibiting miR-625, and then inhibits BC cell pyroptosis.

Preliminary Study on Relationship Between Terminal Ileal Histone Deacetylase 3 Expression and Obesity and Intestinal Flora / 胃肠病学

Background: Histone deacetylase 3 (HDAC3), which is expressed in liver, muscle and adipose tissue, is closely related to fat metabolism. Furthermore, HDAC3 expressed in intestinal epithelial cells is a critical factor that regulates host-commensal flora relationship and maintains intestinal homeostasis. Aims: To investigate the relationship between HDAC3 expression in terminal ileum and obesity and intestinal flora. Methods: Eight SPF C57BL/6 mice and eight germ-free C57BL/6 mice aged six weeks were randomly placed on a standard chow or a high-fat chow, respectively, for 5 weeks. Changes in body weight were recorded weekly, and the terminal ileum was obtained for detection of HDAC3 protein and mRNA expressions by immunohistochemistry and real-time PCR. Results: Increase of body weight of mice in SPF high-fat diet group was much more than that in SPF normal diet group (P0.05). No significant differences were found in HDAC3 protein and mRNA expressions between germ-free high-fat diet group and germ-free normal diet group (P>0.05). Conclusions: Expression of HDAC3 in terminal ileum might be regulated by intestinal flora and participates in the occurrence of obesity.

Histone Deacetylase-3 Modification of MicroRNA-31 Promotes Cell Proliferation and Aerobic Glycolysis in Breast Cancer and Is Predictive of Poor Prognosis / 한국유방암학회지

PURPOSE: The incidence and mortality of breast cancer is increasing worldwide. There is a constant quest to understand the underlying molecular biology of breast cancer so as to plan better treatment options. The purpose of the current study was to characterize the expression of histone deacetylases-3 (HDAC3), a member of class I HDACs, and assess the clinical significance of HDAC3 in breast cancer. METHODS: Quantitative real-time polymerase chain reaction, immunohistochemistry, and western blot analysis were used to examine messenger RNA and protein expression levels. The relationships between HDAC3 expression and clinicopathological variables were analyzed. MTT assays were used to detect cell proliferation. Glucose-uptake, lactate, adenosine triphosphate, and lactate dehydrogenase assays were employed to detect aerobic glycolysis. Chromatin immunoprecipitation was used to detect microRNA-31 (miR-31) promoter binding. RESULTS: Our data revealed that HDAC3 was upregulated in breast cancer tissue compared with matched para-carcinoma tissues, and high levels of HDAC3 were positively correlated with advanced TNM stage and N stage of cancer. Furthermore, overexpression of HDAC3 promoted breast cancer cell-proliferation and aerobic glycolysis. The functional involvement of HDAC3 was related in part to the repression of miR-31 transcription via decreased histone H3 acetylation at lysine K9 levels of the miR-31 promoter. Survival analysis revealed that the level of HDAC3 was an independent prognostic factor for breast cancer patients. CONCLUSION: Our findings revealed that HDAC3 served as an oncogene that could promote cell proliferation and aerobic glycolysis and was predictive of a poor prognosis in breast cancer. HDAC3 participated in the cell proliferation of breast cancer, which may prove to be a pivotal epigenetic target against this devastating disease.

Effect of erythromycin on cigarette smoke-induced histone deacetylase-3 protein expression in human macrophages / 中国免疫学杂志

Objective:To study the effect of erythromycin(EM) on cigarette smoke-induced histone deacetylase-3(HDAC3) protein expression in human macrophages in vitro .Methods:The Aqueous cigarette smoke extract ( CSE) was always prepared fresh on the day of the experiment .The U937 monocytic cells were differentiated into macrophages by using phorbol 12-myristate 13-acetate (PMA) according to standard procedures .The U937 differentiated cells were treated with either CSE (1%) or EM (1 μg/ml) pre-treatment, and HDAC inhibitor trichostatin A (TSA;100 ng/ml) for 24 h.HDAC activity was measured with a colorimetric assay kit and Western blot was used for HDAC3 and factor nuclear-kappaB (NF-κB) protein assays.The levels of tumor necrosis factor-α(TNF-α) release in the supernatant were determined by enzyme linked immunosorbent assay (ELISA).Results:CSE(1%) significantly de-creased HDAC activity and HDAC 3 protein levels at 24 h.Preincubation with EM (1μg/ml ) for 24 h significantly inhibit CSE (1%) induced decrease of HDAC3 protein expression.Furthermore, Preincubation with EM(1 μg/ml) for 24 h significantly inhibit NF-κB activity and TNF-αrelease in human macrophages .Conclusion:EM is able to restore HDAC3 levels decreased by cigarette smoke and inhibit NF-κB activity resulting in decreasing CSE-mediated TNF-αrelease, which has shown an important explanation that EM possess the anti-inflammatory effect induced by cigarette smoke .

Predictive value of serum HDAC3,CysC and albumin levels on a large area of myocardial infarction / 重庆医学

Objective To investigate the predictive value of serum histone deacetylase 3(HDAC3) ,cystatin C(CysC) and albu‐min levels on a large area of myocardial infarction .Methods According to whether heart failure and (or) cardiogenic shock occur‐ring during hospitalization ,102 patients with acute myocardial infarction(AMI) were divided into the two groups :the non - compli‐cating heart failure and (or) cardiogenic shock group(n= 63) and the complicating heart failure and (or) cardiogenic shock group(n= 39) .Then according to whether the creatine kinase(CK‐MB) peak value was greater than 200 IU /L ,102 AMI patients were di‐vided into two groups :CK‐MB peak values ≥ 200 IU /L group(n= 58) and the CK‐MB peak values 200 IU /L group were significantly increased (P< 0 .01) ,while serum albumin level was significantly decreased(P< 0 .01) .Conclusion Serum HDAC3 ,CysC and albumin levels have certain predictive value on a large area of myocardial infarction and conduce to judge the prognosis of patients .