Overexpression of Histone Deacetylase and Amyloid Precursor Protein in Hepatocellular Carcinoma

Zhao, Luguang; He, Dan; Jiao, Mengmeng; Kong, Lingshuo; Shao, Chun-Kui; Chen, Junli; Fang, Zhigang; Ma, Xing-Hong; Chen, Huifang; Lin, Lynlee L.; Luo, Si; Chen, Yunbo; Wang, Qi; Fang, Shuhuan

doi:10.1177/1533034616661664

Cited by 8 publications

(4 citation statements)

References 33 publications

(43 reference statements)

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“…Moreover, histone deacetylases are associated with the development of many cancers. Knockdown of HDAC1 resulted in APP downregulation, caspase-7 cleavage, and apoptosis, which demonstrates an association between APP expression and the regulation of HDAC1 [ 58 ].…”

Section: Amyloid Precursor Protein In Cancermentioning

confidence: 99%

Molecular Characteristics of Amyloid Precursor Protein (APP) and Its Effects in Cancer

Lee

Jeong

Jang

2021

IJMS

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Amyloid precursor protein (APP) is a type 1 transmembrane glycoprotein, and its homologs amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are highly conserved in mammals. APP and APLP are known to be intimately involved in the pathogenesis and progression of Alzheimer’s disease and to play important roles in neuronal homeostasis and development and neural transmission. APP and APLP are also expressed in non-neuronal tissues and are overexpressed in cancer cells. Furthermore, research indicates they are involved in several cancers. In this review, we examine the biological characteristics of APP-related family members and their roles in cancer.

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Section: Amyloid Precursor Protein In Cancermentioning

confidence: 99%

Molecular Characteristics of Amyloid Precursor Protein (APP) and Its Effects in Cancer

Lee

Jeong

Jang

2021

IJMS

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“…Rikimaru et al advocated that in human HCC, increased expression of HDAC1 was associated with higher invasiveness, lower differentiation, and poor prognosis (26). In contrast, Zhao et al claimed that expression of HDAC1 was significantly higher in HCC tissues than that in adjacent tissues, but there was no statistical difference between HDAC1 with tumor stage (27) …”

Section: Hypoacetylation Of Histone H3 In Human Hccmentioning

confidence: 99%

Cytokeratin 18-associated Histone 3 Modulation in Hepatocellular Carcinoma: A Mini Review

Lai

Cheng

Lai

et al. 2017

CGP

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Abstract.Hepatocellular carcinoma (HCC) is a cancer with high incidence and mortality in Taiwan. HCC cells exhibit different morphological features in divergent shapes and having pleomorphic nuclei from normal liver cells. Microtubules (MTs), intermediate filaments (IFs), and microfilaments (MFs) are major components of the cytoskeleton that are essential to maintain the integrity of eukaryotic cells (1). Proper cross-linking structures among these cytoskeletal proteins are crucial for intracellular architectures and normal cellular morphology. Plectin exhibits the binding sites accessible to IFs, MTs and MFs rendering the interaction with a variety of cytoskeletal components to maintain the integrity of the cytoskeletal network (2). The rope-like IFs have a mean diameter of 10 nm and mainly play a role in maintaining the shape and mechanical integrity of a cell (3). In human hepatocytes, a cytokeratin (CK) pair composed of CK8 (type II, 52 kD) and CK18 (type I, 45 kD) renders IFs (4). CKs are required for maintaining the integrity of hepatocytes (5). Altered expression of keratin genes were associated with chronic hepatitis, increased hepatocyte fragility and decreased bile secretion (6).In eukaryotic nucleus, the organization and packaging of DNA are achieved by addition of histone proteins to form chromatin. Post-translational modifications of histones, such as acetylation, phosphorylation, methylation and ADPribosylation, frequently alter the structure of chromatin (7). Epigenetic modifications of histone, especially acetylation status, altering the chromatin structure are involved in gene expression and further intervened in the pathogenesis of cancer. Two types of enzymes, including histone acetyltransferases (HATs) and histone deacetylases (HDACs), affect the acetylation status of histones. Recently it was reported that alterations in the activities of HDACs, as well as aberrant acetylation of histone, lead to diseases including cancer (8). HDACs catalyze histone deacetylation and repress transcription of specific genes, such as p21, resulting in cell-cycle activation and cell proliferation (9).The investigation of histones in our laboratory originated in a study of CK18, in which we found that CK18 was coimmunoprecipitated with histone H3 in human HCC, but not in normal liver. We speculated that both histone H3 and CK18 were modulated in HCC, which was shown in the co-219

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“…(‐)‐epigallocatechin‐3‐gallate (EGCG), which comprises more than 50% of total polyphenols in green tea, 27 has numerous potential chemo‐preventive and therapeutic functions for various tumours 28,29 . EGCG is a natural HDACi that can induce apoptosis via epigenetic modification as demonstrated in cancerous cells 30 . Thus, it could be a potential natural HDACi that may be applied for cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

“… 28 , 29 EGCG is a natural HDACi that can induce apoptosis via epigenetic modification as demonstrated in cancerous cells. 30 Thus, it could be a potential natural HDACi that may be applied for cancer treatment. In addition, some studies showed that EGCG induces apoptosis in cancer cells through acetylation of Ku70 and can cause dissociation of the Bax/Ku70 complex as shown in lung cancer.…”

Section: Introductionmentioning

confidence: 99%

(‐)‐Epigallocatechin‐3‐gallate induced apoptosis by dissociation of c‐FLIP/Ku70 complex in gastric cancer cells

Shahriari Felordi,

Alikhani,

Farzaneh

et al. 2023

J Cellular Molecular Medi

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Anti‐cancer properties of (‐)‐epigallocatechin‐3‐gallate (EGCG) are mediated via apoptosis induction, as well as inhibition of cell proliferation and histone deacetylase. Accumulation of stabilized cellular FLICE‐inhibitory protein (c‐FLIP)/Ku70 complex in the cytoplasm inhibits apoptosis through interruption of extrinsic apoptosis pathway. In this study, we evaluated the anti‐cancer role of EGCG in gastric cancer (GC) cells through dissociation of c‐FLIP/Ku70 complex. MKN‐45 cells were treated with EGCG or its antagonist MG149 for 24 h. Apoptosis was evaluated by flow cytometry and quantitative RT‐PCR. Protein expression of c‐FLIP and Ku70 was analysed using western blot and immunofluorescence. Dissociation of c‐FLIP/Ku70 complex as well as Ku70 translocation were studied by sub‐cellular fractionation and co‐immunoprecipitation. EGCG induced apoptosis in MKN‐45 cells with substantial up‐regulation of P53 and P21, down‐regulation of c‐Myc and Cyclin D1 as well as cell cycle arrest in S and G2/M check points. Moreover, EGCG treatment suppressed the expression of c‐FLIP and Ku70, decreased their interaction while increasing the Ku70 nuclear content. By dissociating the c‐FLIP/Ku70 complex, EGCG could be an alternative component to the conventional HDAC inhibitors in order to induce apoptosis in GC cells. Thus, its combination with other cancer therapy protocols could result in a better therapeutic outcome.

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Overexpression of Histone Deacetylase and Amyloid Precursor Protein in Hepatocellular Carcinoma

Cited by 8 publications

References 33 publications

Molecular Characteristics of Amyloid Precursor Protein (APP) and Its Effects in Cancer

Molecular Characteristics of Amyloid Precursor Protein (APP) and Its Effects in Cancer

Cytokeratin 18-associated Histone 3 Modulation in Hepatocellular Carcinoma: A Mini Review

(‐)‐Epigallocatechin‐3‐gallate induced apoptosis by dissociation of c‐FLIP/Ku70 complex in gastric cancer cells

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