Histone deacetylase 5 promotes the migration and invasion of hepatocellular carcinoma via increasing the transcription of hypoxia-inducible factor-1α under hypoxia condition

Ye, Ming; Fang, Zejun; Gu, Hongqian; Song, Rui; Ye, Jiangwei; Li, Hongzhang; Wu, Zhiguang; Zhou, Shenghui; Cai, Xiang; Ding, Xiaokun; Yu, Songshan

doi:10.1177/1010428317705034

Cited by 19 publications

(20 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Acetylation is an important posttranslational modification of a protein. This modification is found widely in eukaryotic cells and occurs during the physiological activities at various stages (Kimura et al, 2005;Ishfaq et al, 2012;Lu et al, 2014), from regulating the function of proteins, especially in terms of protein stability (Zhou et al, 2016), to intracellular signal transduction (Batta et al, 2007;Tang et al, 2007;Spange et al, 2009), disease and other physiological processes (Batta et al, 2007;Iyer et al, 2012;Marouco et al, 2013;Ye et al, 2017). Acetylation occurs on the ε-amino group of lysine residues (Lu et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

The effect of acetylation on the protein stability of BmApoLp‐III in the silkworm, Bombyx mori

Yang

Zhu

Liu

et al. 2019

Insect Molecular Biology

View full text Add to dashboard Cite

Acetylation is an important, reversible posttranslational modification to a protein. In a previous study, we found that there were a large number of acetylated sites in various nutrient storage proteins of the silkworm haemolymph. In this study, we confirmed that acetylation can affect the stability of nutrient storage protein Bombyx mori apolipophorin‐III (BmApoLp‐III). First, the expression of BmApoLp‐III could be upregulated when BmN cells were treated with the deacetylase inhibitor panobinostat (LBH589); similarly, the expression was downregulated when the cells were treated with the acetylase inhibitor C646. Furthermore, the increase in acetylation by LBH589 could inhibit the degradation and improve the accumulation of BmApoLp‐III in BmN cells treated with cycloheximide and MG132 respectively. Moreover, we found that an increase in acetylation could decrease the ubiquitination of BmApoLp‐III and vice versa; therefore, we predicted that acetylation could improve the stability of BmApoLp‐III by competing for ubiquitination and inhibiting the protein degradation pathway mediated by ubiquitin. Additionally, BmApoLp‐III had an antiapoptosis function that increased after LBH589 treatment, which might have been due to the improved protein stability after acetylation. These results have laid the foundation for further study on the mechanism of acetylation in regulating the storage and utilization of silkworm nutrition.

show abstract

Section: Introductionmentioning

confidence: 99%

The effect of acetylation on the protein stability of BmApoLp‐III in the silkworm, Bombyx mori

Yang

Zhu

Liu

et al. 2019

Insect Molecular Biology

View full text Add to dashboard Cite

show abstract

“…By bioinformatics analysis and microarray technology, functions of some differentially expressed genes (DEGs) in HCC have been explored, which paved the way for exploring complicated process in the occurrence and development of HCC [ 5 , 7 – 9 ]. As an important part of participating in life activities, transcription factors (TFs) have been reported to play an important role in the development of HCC by numerous studies [ 10 , 11 ]. A work by S. Hua et al found that ETS1, a cancer-related TF, could through interaction with miR-139-5p inhibit cell proliferation, migration, and invasion in HCC [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Transcription Factor-Related Regulatory Networks Based on Bioinformatics Analysis and Validation in Hepatocellular Carcinoma

Shui

Yao

Zhang

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) accounts for a significant proportion of liver cancer, which has become the second most common cause of cancer-related mortality worldwide. To investigate the potential mechanisms of invasion and progression of HCC, bioinformatics analysis and validation by qRT-PCR were performed. We found 237 differentially expressed genes (DEGs) including EGR1, FOS, and FOSB, which were three cancer-related transcription factors. Subsequently, we constructed TF-gene network and miRNA-TF-mRNA network based on data obtained from mRNA and miRNA expression profiles for analysis of HCC. We found that 42 key genes from the TF-gene network including EGR1, FOS, and FOSB were most enriched in the p53 signaling pathway. The qRT-PCR data confirmed that mRNA levels of EGR1, FOS, and FOSB all were decreased in HCC tissues. In addition, we confirmed that the mRNA levels of CCNB1, CCNB2, and CHEK1, three key markers of the p53 signaling pathway, were all increased in HCC tissues by bioinformatics analysis and qRT-PCR validation. Therefore, we speculated that miR-181a-5p, which was upregulated in HCC tissues, could regulate FOS and EGR1 to promote the invasion and progression of HCC by p53 signaling pathway. Overall, the study provides support for the possible mechanisms of progression in HCC.

show abstract

“…Here, poor clinical outcome, i.e., low overall and disease-free survival, was associated with overexpression of HDAC5 in pNET tissue [ 21 ]. Additionally, expression changes of HDAC5 were found, e.g., in hepatocellular carcinoma [ 22 , 23 ], lung cancer [ 24 ], and colon cancer [ 25 ], thus underlining its role in oncogenesis. Several studies, additionally, have shown a significant cytotoxic effect of various HDAC inhibitors (mostly pan-HDAC specificity) in pNET cell lines in vitro [ 26 , 27 , 28 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Inhibition of Class IIA HDACs by LMK-235 in Pancreatic Neuroendocrine Tumor Cells

Wanek

Gaisberger

Beyreis

et al. 2018

IJMS

View full text Add to dashboard Cite

Histone deacetylases (HDACs) play a key role in epigenetic mechanisms in health and disease and their dysfunction is implied in several cancer entities. Analysis of expression patterns in pancreatic neuroendocrine tumors (pNETs) indicated HDAC5 to be a potential target for future therapies. As a first step towards a possible treatment, the aim of this study was to evaluate the in vitro cellular and molecular effects of HDAC5 inhibition in pNET cells. Two pNET cell lines, BON-1 and QGP-1, were incubated with different concentrations of the selective class IIA HDAC inhibitor, LMK-235. Effects on cell viability were determined using the resazurin-assay, the caspase-assay, and Annexin-V staining. Western Blot and immunofluorescence microscopy were performed to assess the effects on HDAC5 functionality. LMK-235 lowered overall cell viability by inducing apoptosis in a dose- and time-dependent manner. Furthermore, acetylation of histone-H3 increased with higher LMK-235 concentrations, indicating functional inhibition of HDAC4/5. Immunocytochemical analysis showed that proliferative activity (phosphohistone H3 and Ki-67) decreased at highest concentrations of LMK-235 while chromogranin and somatostatin receptor 2 (SSTR2) expression increased in a dose-dependent manner. HDAC5 expression was found to be largely unaffected by LMK-235. These findings indicate LMK-235 to be a potential therapeutic approach for the development of an effective and selective pNET treatment.

show abstract

Histone deacetylase 5 promotes the migration and invasion of hepatocellular carcinoma via increasing the transcription of hypoxia-inducible factor-1α under hypoxia condition

Cited by 19 publications

References 29 publications

The effect of acetylation on the protein stability of BmApoLp‐III in the silkworm, Bombyx mori

The effect of acetylation on the protein stability of BmApoLp‐III in the silkworm, Bombyx mori

Analysis of Transcription Factor-Related Regulatory Networks Based on Bioinformatics Analysis and Validation in Hepatocellular Carcinoma

Pharmacological Inhibition of Class IIA HDACs by LMK-235 in Pancreatic Neuroendocrine Tumor Cells

Contact Info

Product

Resources

About