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Increased expression of histone deacetylases (HDACs) affiliated to the epigenetic regulation is common aberration in prostate cancer (PCa). We have confirmed that hepatocyte cell adhesion molecule (hepaCAM), acting as a tumor suppressor gene, is rarely expressed in PCa previously, However, the mechanisms of which is still unknown. The level of histone acetylation reportedly may involve anti-oncogene transcription and expression. In this study, we investigated the effect of panobinostat, the broad-spectrum histone deacetylases inhibitor, on PCa LNCaP and DU145 cell growth, and observed re-expression of hepaCAM when treated with panobinostat. We demonstrated that intranuclear acetylation of lys9 of histone H3 (Ac-H3K9) were increased, while that of both mRNA and protein of HDAC1, HDAC3, and HDAC4 were decreased when the treating concentration of panobinostat increased. We confirmed the relationship between histone acetylation and the expression of hepaCAM and AR in prostate cancer tissues. We also confirmed that panobinostat could overcome the resistance for androgen deprivation therapy (ADT). Further, we combined panobinostat with Ad-hepaCAM, which resulted in significantly increased antitumor activity and significant attenuation of the proliferation-associated genes CCND1 and PCNA compared to each single treatment. In conclusion, panobinostat may enhance the acetylation of lys9 of histone 3 and reverse the hepaCAM expression through its inhibitory effect on HDACs activity in PCa LNCaP and DU145 cells; Ad-hepaCAM combined with panobinostat may synergistically inhibit the growth of LNCaP and DU145 cells, via a potential mechanism associated with the down-regulation of the expression of CCND1 and PCNA. These findings suggest that this therapeutic strategy should be further developed in clinical trials., (Copyright © 2021. Published by Elsevier B.V.)

Histone deacetylases (HDACs) play essential roles in modulating chromatin structure to provide accessibility to gene regulators. Increasing evidence has linked HADCs to pathogenesis control in the filamentous plant fungi. However, its function remains unclear in Fusarium pseudograminearum, which has led to the emergence of the disease Fusarium crown rot in China. Here we identified the FpDEP1 gene, an orthologue of Saccharomyces cerevisiae DEP1 encoding a component of the Rpd3 histone deacetylase complex in F. pseudograminearum. The gene deletion mutant, ΔFpdep1, showed significantly retarded growth on PDA plates with reduced aerial hyphae formation. Pathogenicity tests displayed no typical leaf lesions and limited expansion capability of coleoptiles. Histopathological analysis indicated the ΔFpdep1 deletion mutant differentiated infectious hyphae and triggered massive reactive oxygen species (ROS) accumulation during the early infection stage, resulting in limited expansion to neighbor cells which was concurring with sensitivity to H 2 O 2 and SDS tests in vitro. FM4-64 staining revealed that the ΔFpdep1 deletion mutant was delayed in endocytosis. The FpDEP1-GFP transgene complemented the mutant phenotypes and the fusion protein co-localized with DAPI staining, indicating that the FpDEP1 gene product is localized to the nucleus in spores and mycelia. Immunoprecipitation coupled with LC-MS/MS and yeast two-hybrid screening identified the Rpd3L-like HDAC complex containing at least FpDep1, FpSds3, FpSin3, FpRpd3, FpRxt3, FpCti6, FpRho23, and FpUme6. These results suggest that FpDep1 is involved in a HDAC complex functioning on fungal development and pathogenesis in F. pseudograminearum., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

BACKGROUND Peritoneal dialysis is the most common treatment for end-stage renal disease. However, peritoneal fibrosis resulting from long-term peritoneal dialysis restricts peritoneal ultrafiltration. Previous studies have shown a role for 1,25-dihydroxyvitamin D3 (1,25[OH]₂D3) in preventing fibrosis, but the potential mechanisms remain unknown. This study aimed to investigate the role of 1,25(OH)₂D3 in epithelial-mesenchymal transition (EMT) and the downstream signaling pathway in HMrSV5 human peritoneal mesothelial cells in vitro. MATERIAL AND METHODS An in vitro cell model of peritoneal fibrosis was established using the HMrSV5 human peritoneal mesothelial cell line. High glucose and lipopolysaccharide (LPS) culture conditions, with or without 1,25(OH)₂D3, were used. Wnt agonist 1, a Wnt signaling pathway activator, was applied. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to measure the vitamin D receptor (VDR) and histone deacetylase 3 (HDAC3) gene and protein expression levels, ß-catenin, and EMT-associated biomarkers. RESULTS High glucose plus LPS culture medium inhibited cell proliferation, induced cell apoptosis and promoted EMT in HMrSV5 cells, which was reversed by 1,25(OH)₂D3 by down-regulation of HDAC3 and upregulation of VDR. HDAC3 inhibited VDR gene expression. The expression of EMT-associated biomarkers was increased by Wnt agonist 1 and inhibited by 1,25(OH)₂D3. CONCLUSIONS In HMrSV5 human peritoneal mesothelial cells, 1,25(OH)₂D3 reversed EMT by inhibiting the expression of HDAC3 and upregulating VDR gene expression via the Wnt/ß-catenin signaling pathway.

Schizophrenia (SCZ) is a complex neuropsychiatric disorder with high heritability. Abnormal gene methylation was found to play a key role in the development of SCZ, suggesting that histone deacetylases (HDACs) may increase the expression of several key genes in the brain. However, recent studies evaluating the association between SCZ and genetic polymorphisms in histone deacetylase 3 (encoded by HDAC3) have shown conflicting results. In this study, we designed a two-stage case-control study to investigate the association of the HDAC3 with SCZ. Fourteen tag single nucleotide polymorphisms (SNPs) entirely covering the region of HDAC3 were analyzed in the testing group of 1,421 patients and 2,823 healthy controls, and the SNP rs14251 was found to be significant (and rs2530223 to be nominally significant). The significant result of rs14251 was successfully replicated in the validation group consisting of 896 cases and 1,815 healthy controls (P = 0.009276, OR = 1.219), and also confirmed by haplotype based analyses (rs976552-rs14251, global P < 0.001). To sum up, our results provide additional evidence that HDAC3 confers the increasing risk of SCZ susceptibility in Han Chinese individuals, suggesting this gene as a potential genetic modifier for SCZ development. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Metastasis-associated gene 1 (MTA1), which is involved in tumor progression, metastasis, and angiogenesis, has been examined in several malignant tumors. However, the expression and the effect of MTA1 on human cervical cancer remain unknown. In this study, we investigated the level of MTA1 expression in cervical carcinoma and its clinical significance. By immunohistochemical staining, the correlation of MTA1 overexpression with clinical features and patient outcome was analyzed in 132 formalin-fixed, paraffin-embedded cervical cancer tissues. MTA1 protein overexpression was detected in 73 (55.3%) of 132 patients. High levels of MTA1 protein were clearly correlated with histologic grade (P = .006), lymph node metastasis (P = .001), and recurrence (P = .016). Multivariate Cox analysis showed that MTA1 was an independent factor for overall survival (hazard ratio, 3.486; 95% confidence interval [CI], 1.274-9.537; P = .015) and disease-free survival (hazard ratio, 3.373; 95% CI, 1.212-9.387; P = .020). Multivariate logistic regression analysis indicated that elevated MTA1 was strongly associated with lymph node metastasis (odds ratio, 3.879; 95% CI, 1.391-10.816; P = .010). Sensitivity and specificity were calculated as 81.25% and 53.0%, respectively. These findings suggest that MTA1 nuclear overexpression is associated with tumor progression and metastasis and thus support its clinical significance in future gene-targeted therapies, particularly the management of patients with cervical cancer., (Copyright © 2013 Elsevier Inc. All rights reserved.)