RESUMO
Mindin is important in broad spectrum of immune responses. On the other hand, we previously reported that mindin attenuated human colon cancer development by blocking angiogenesis through Egr-1-mediated regulation. However, the mice original mindin directly suppressed the syngenic colorectal cancer (CRC) growth in our recent study and we aimed to further define the role of mindin during CRC development in mice. We established the mouse syngeneic CRC CMT93 and CT26 WT cell lines with stable mindin knock-down or overexpression. These cells were also subcutaneously injected into C57BL/6 and BALB/c mice as well as established a colitis-associated colorectal cancer (CAC) mouse model treated with lentiviral-based overexpression and knocked-down of mindin. Furthermore, we generated mindin knockout mice using a CRISPR-Cas9 system with CAC model. Our data showed that overexpression of mindin suppressed cell proliferation in both of CMT93 and CT26 WT colon cancer cell lines, while the silencing of mindin promoted in vitro cell proliferation via the ERK and c-Fos pathways and cell cycle control. Moreover, the overexpression of mindin significantly suppressed in vivo tumour growth in both the subcutaneous transplantation and the AOM/DSS-induced CAC models. Consistently, the silencing of mindin reversed these in vivo observations. Expectedly, the tumour growth was promoted in the CAC model on mindin-deficient mice. Thus, mindin plays a direct tumour suppressive function during colon cancer progression and suggesting that mindin might be exploited as a therapeutic target for CRC.
Assuntos
Neoplasias do Colo/genética , Proteínas da Matriz Extracelular/genética , Genes Supressores de Tumor/fisiologia , Sistema de Sinalização das MAP Quinases/genética , Transdução de Sinais/genética , Animais , Ciclo Celular/genética , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Colite/genética , Colite/patologia , Colo/patologia , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Progressão da Doença , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Células RAW 264.7RESUMO
Trefoil factor 1 (TFF1), a member of the trefoil peptide family, is not only associated with mucosal protection and restoration but is also correlated with tumorigenesis of the gastrointestinal tract. In an early study, we performed sequence analysis and identified one potential miR423-5p binding site within the 3'-untranslated region of TFF1 using microRNA target prediction tools. In the current study, we demonstrated that the coding DNA region within TFF1 is also a candidate for miR218-5p targeting. We used real-time PCR and in situ hybridization to analyze the correlation between miR218-5p and TFF1 expression in tumor lesions and paracancerous tissue in gastric cancer (GC) samples. Additionally, endogenous and exogenous TFF1 were suppressed by miR218-5p in gastric cancer cells and influenced the progression of GC in an Erk1/2-dependent manner. Targeting miR218-5p may provide a novel strategy for the treatment of GC.
Assuntos
Proliferação de Células/genética , MicroRNAs/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neoplasias Gástricas/genética , Proteínas Supressoras de Tumor/genética , Animais , Sequência de Bases , Western Blotting , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização In Situ , Camundongos Nus , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência do Ácido Nucleico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Transplante Heterólogo , Fator Trefoil-1 , Carga Tumoral/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
Chronic inflammation, such as that seen in patients with inflammatory bowel disease (IBD), greatly increases the risk of developing colon cancer. Growing evidence supports a role for T cell-mediated immune response and release of various cytokines in the pathogenesis of colitis-associated cancer (CAC). In fact, CD4+ effector T cells promote chronic inflammation associated with IBD through release of proinflammatory cytokines, which leads to initiation and progression of colon cancer. Furthermore, CD8+ T cells reduce tumor growth through cancer immunosurveillance, which can also contribute to intestinal inflammation and thereby might promote tumor growth. In contrast, regulatory T cells (Tregs) release the immunosuppressive cytokines IL-10, TGF-ß and thus have protective effects in CAC. In addition, dendritic cells (DCs) are important components of antitumor immunity. Recently, a novel mouse model that was associated with repeated inflammation was established for investigating the immunopathogenesis of CAC. This review discusses the role of T cell-mediated immune response, and DCs and involved cytokines in the immunopathogenesis of CAC in an animal model, which may also provide future therapeutic targets in CAC.
Assuntos
Colite/induzido quimicamente , Modelos Animais de Doenças , Imunidade Celular/imunologia , Neoplasias/etiologia , Neoplasias/patologia , Linfócitos T Reguladores/imunologia , Animais , Colite/metabolismo , Colite/patologia , Citocinas/metabolismo , Humanos , Camundongos , Neoplasias/metabolismoRESUMO
Chronic infection with hepatitis B virus is a cause of end-stage liver disease and hepatocellular carcinoma (HCC). We previously screened fructose-bisphosphate aldolase B (ALDOB) as a candidate binding protein of hepatitis B surface antigen (HBsAg) using a yeast 2-hybrid assay. In this study we aimed to confirm ALDOB as a binding protein of the S region of the HbsAg (HBs) and to investigate the function and involved mechanism between its interactions during HCC development. Our results demonstrated that both of exogenous and endogenous ALDOB proteins bind to HBs and colocalize in the cytoplasm in vitro. The coexistence of HBs and ALDOB inhibit apoptosis of cisplatin-induced HepG2 cells. Furthermore, western blot analysis showed the coexistence of HBs and ALDOB enhance the phosphorylations of AKT and its downstream of GSK-3ß (phosphorylation); decreased expression of the pro-apoptotic proteins Bax, Bid, Bim, and Puma; and increased expression of the prosurvival proteins Bcl-2, Bcl-xl, and Mcl-1 in HepG2 cells. These findings suggest that interaction between HBs and ALDOB might be applied as a potential therapeutic target during the treatment of HBV-related hepatitis or HCC.
Assuntos
Apoptose/fisiologia , Carcinoma Hepatocelular/patologia , Cisplatino/farmacologia , Frutose-Bifosfato Aldolase/metabolismo , Antígenos de Superfície da Hepatite B/metabolismo , Neoplasias Hepáticas/patologia , Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/biossíntese , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/biossíntese , Proteína 11 Semelhante a Bcl-2 , Carcinoma Hepatocelular/virologia , Linhagem Celular Tumoral , Frutose-Bifosfato Aldolase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Células HEK293 , Células Hep G2 , Vírus da Hepatite B , Hepatite B Crônica , Humanos , Neoplasias Hepáticas/virologia , Proteínas de Membrana/biossíntese , Proteína de Sequência 1 de Leucemia de Células Mieloides/biossíntese , Fosforilação , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno , Proteína X Associada a bcl-2/biossíntese , Proteína bcl-X/biossínteseRESUMO
BACKGROUND: Trefoil factor family 1 (TFF1) is a member of the TFF-domain peptide family involved in epithelial restitution and cell motility. Recently, we screened Piezo1 as a candidate TFF1-binding protein. AIM: We aimed to confirm Piezo1 as a novel TFF1 binding protein and to assess the role of this interaction in mediating gastric cancer cell mobility. METHODS: This interaction was confirmed by co-immunoprecipitation and co-localisation of TFF1 and Piezo1 in GES-1 cells. We used stable RNA interference to knockdown Piezo1 protein expression and restored the expression of TFF1 in the gastric cancer cell lines SGC-7901 and BGC-823. Cell motility was evaluated using invasion assay and migration assay in vitro. The expression levels of the integrin subunits ß1, ß5, α1 as well as the expression of ß-catenin and E-cadherin were detected by Western blot. RESULTS: We demonstrate that TFF1, but not TFF2 or TFF3, bind to and co-localize with Piezo1 in the cytoplasm in vitro. TFF1 interacts with the C-terminal portion of the Piezo1 protein. Wound healing and trans-well assays demonstrated that the restored expression of TFF1 promoted cell mobility in gastric cancer cells, and this effect was attenuated by the knockdown of Piezo1. Western blots demonstrated the decreased expression of integrin ß1 in Piezo1-knockdown cells. CONCLUSIONS: Our data demonstrate that Piezo1 is a novel TFF1 binding protein that is important for TFF1-mediated cell migration and suggest that this interaction may be a therapeutic target in the invasion and metastasis of gastric cancer.
Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Transporte/metabolismo , Movimento Celular/fisiologia , Canais Iônicos/metabolismo , Neoplasias Gástricas/fisiopatologia , Proteínas Supressoras de Tumor/metabolismo , Western Blotting , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Imunoprecipitação , Neoplasias Gástricas/metabolismo , Fator Trefoil-1 , Fator Trefoil-2RESUMO
BACKGROUND: As a secreted protein, serum trefoil factor 3 (TFF3) has been reported to be a biomarker of several malignancies. We further investigated whether TFF3 can be applied as a biomarker for and predictor of responses to chemotherapy in gastrointestinal cancer. METHODS: Serum and urine samples were collected from 90 patients with gastric cancer, 128 patients with colorectal cancer and 91 healthy individuals. Serum and urine TFF3 levels were measured using an ELISA. RESULTS: Serum and urine TFF3 levels were significantly higher in the patients with gastric and colorectal cancer compared with the healthy individuals (P < 0.05). Higher serum levels of TFF3 were significantly correlated with distant metastasis and an advanced stage in the two types of cancer (P < 0.05). Age and the number of lymph node metastases were significantly correlated with serum TFF3 levels in colorectal cancer, and decreased serum TFF3 levels were significantly correlated with responses to chemotherapy in both the gastric and the colorectal cancer partial response (PR) groups. A combination of serum and urine data did not significantly improve the detection of either cancer, although urine levels have shown a significant negative relationship with the glomerular filtration rate (GFR). CONCLUSIONS: Our data indicate that TFF3 may be an effective biomarker of tumor stage and the presence of distant metastasis, and may be a pharmacodynamic marker of response to chemotherapy in gastrointestinal cancer.
Assuntos
Antivirais/uso terapêutico , Transplante de Microbiota Fecal , Antígenos E da Hepatite B/análise , Hepatite B Crônica/terapia , Hepatite B Crônica/virologia , Adulto , Estudos de Casos e Controles , Feminino , Microbioma Gastrointestinal/imunologia , Hepatite B Crônica/imunologia , Humanos , MasculinoRESUMO
A total of ~38.6 million mortalities occur due to liver cancer annually, worldwide. Although a variety of therapeutic methods are available, the efficacy of treatment at present is extremely limited due to an increased risk of malignancy and inherently poor prognosis of liver cancer. Gene therapy is considered a promising option, and has shown notable potential for the comprehensive therapy of liver cancer, in keeping with advances that have been made in the development of cancer molecular biology. The present study aimed to investigate the synergistic effects of the abilities of the hemagglutinin neuraminidase protein of Newcastle disease virus (NDV), the pro-apoptotic factor apoptin from chicken anaemia virus, and the interferon-γ inducer interleukin-18 (IL-18) in antagonizing liver cancer. Therefore, a recombinant DNA plasmid expressing the three exogenous genes, VP3, IL-18 and hemagglutinin neuraminidase (HN), was constructed. Flow cytometry, acridine orange/ethidium bromide staining and analysis of caspase-3 activity were performed in H22 cell lines transfected with the recombinant DNA plasmid. In addition, 6-week-old C57BL/6 mice were used to establish a H22 hepatoma-bearing mouse model. Mice tumor tissue was analyzed by immunohistochemistry and scanning electron microscopy. The results of the present study revealed that the recombinant DNA vaccine containing the VP3, IL-18 and HN genes inhibited cell proliferation and induced autophagy via the mitochondrial pathway in vivo and in vitro.
RESUMO
The pathogenesis of colon cancer (Cca) is to be further investigated. Vitamin D deficiency is associated with cancer growth; the underlying mechanism is unclear. Published data indicate that Cca cells express CD23. This study tests a hypothesis that exposure to IgE induces Cca cell apoptosis. In this study, the effect of ligation of CD23 by IgE on the expression of cyp27b1 was performed with Cca cells. The induction of apoptosis of Cca cells by IgE was assessed in a cell culture model. We observed that Cca cells express CD23; ligation of CD23 with IgE on Cca cells increased the expression of cyp27b1 in Cca, which promoted the conversion of VD3 to calcitriol, the latter increased the expression of FasL by Cca cells, and induced apoptosis of Cca cells. In conclusion, IgE is capable of inducing the cancer cell apoptosis via ligating CD23 and converting VD3 to calcitriol. The results suggest that IgE may have therapeutic potential in the treatment of Cca.
RESUMO
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer mortality. Chemotherapy resistance remains a major challenge for treating advanced CRC. Therefore, the identification of targets that induce drug resistance is a priority for the development of novel agents to overcome resistance. Dragon (also known as RGMb) is a member of the repulsive guidance molecule (RGM) family. We previously showed that Dragon expression increases with CRC progression in human patients. In the present study, we found that Dragon inhibited apoptosis and increased viability of CMT93 and HCT116 cells in the presence of oxaliplatin. Dragon induced resistance of xenograft tumor to oxaliplatinin treatment in mice. Mechanistically, Dragon inhibited oxaliplatin-induced JNK and p38 MAPK activation, and caspase-3 and PARP cleavages. Our results indicate that Dragon may be a novel target that induces drug resistance in CRC.
Assuntos
Moléculas de Adesão Celular Neuronais/biossíntese , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Moléculas de Adesão de Célula Nervosa/biossíntese , Compostos Organoplatínicos/farmacologia , Animais , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Células HCT116 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Oxaliplatina , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Enoyl-coenzyme A hydratase short chain 1 (ECHS1) regulates fatty acid metabolism and is an essential factor in tumor development. The present study aimed to investigate the molecular mechanisms of ECHS1 in hepatocellular carcinogenesis by studying proliferation and survival in ECHS1 knocked-down hepatocellular carcinoma (HCC) cell lines, HepG2 and HuH7. The effect of ECHS1 on tumor development was investigated by tumor transplantation in nude mice, and the signaling pathways involved in the ECHS1-mediated regulation of HCC cell proliferation were identified by western blot analysis. The silencing of ECHS1 suppressed HCC cell proliferation in vitro and suppressed the growth of transplanted tumors in vivo. In addition, the phosphorylation of EGFR and its downstream effectors ERK1/2 and AKT was downregulated in ECHS1 knocked-down cells and tumor tissues. Furthermore, knockdown of ECHS1 in HCC suppressed cyclin D3 and cyclin dependent kinase 6 expression, whilst enhancing p16 and p21 expression. Therefore, ECHS1 may also be involved in cell cycle progression in HCC cells. These results suggested that ECHS1 may promote cell proliferation in HCC in an EGFR-dependent manner.
Assuntos
Carcinogênese , Carcinoma Hepatocelular/genética , Enoil-CoA Hidratase/genética , Receptores ErbB/genética , Neoplasias Hepáticas/genética , Animais , Carcinoma Hepatocelular/patologia , Proliferação de Células/genética , Enoil-CoA Hidratase/biossíntese , Receptores ErbB/biossíntese , Técnicas de Silenciamento de Genes , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Proteína Quinase 3 Ativada por Mitógeno/biossíntese , Proteína Oncogênica v-akt/biossíntese , Fosforilação , Transdução de SinaisRESUMO
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer death. However, the molecular mechanisms underlying CRC initiation, growth and metastasis are poorly understood. Dragon (RGMb), a member of the repulsive guidance molecule (RGM) family, has been recently identified as a co-receptor for bone morphogenetic protein (BMP) signaling, but the role of Dragon in CRC development is undefined. Here, we show that Dragon expression was increased in colon cancer tissues compared to control tissues in CAC mouse model and in human patients. Dragon promoted proliferation of CT26.WT and CMT93 colon cancer cells and accelerated tumor growth in the xenograft mouse model. Dragon's action on colon cancer development was mediated via the BMP4-Smad1/5/8 and Erk1/2 pathways. Therefore, our results have revealed that Dragon is a novel gene that promotes CRC growth through the BMP pathway. Dragon may be exploited as a potential therapeutic target for CRC treatment.
Assuntos
Moléculas de Adesão Celular Neuronais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas do Tecido Nervoso/genética , Animais , Moléculas de Adesão Celular Neuronais/biossíntese , Proliferação de Células/genética , Neoplasias Colorretais/metabolismo , Proteínas Ligadas por GPI , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/biossíntese , Transdução de Sinais , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Previous studies have highlighted the role of genetic predispositions in disease, and several genes had been identified as important in Crohn's disease (CD). However, many of these genes are likely rare and not associated with susceptibility in Chinese CD patients. We found 294 shared identical variants in the CD patients of which 26 were validated by Sanger sequencing. Two heterozygous IFN variants (IFNA10 c.60 T > A; IFNA4 c.60 A > T) were identified as significantly associated with CD susceptibility. The single-nucleotide changes alter a cysteine situated before the signal peptide cleavage site to a stop code (TGA) in IFNA10 result in the serum levels of IFNA10 were significantly decreased in the CD patients compared to the controls. Furthermore, the IFNA10 and IFNA4 mutants resulted in an impairment of the suppression of HCV RNA replication in HuH7 cells, and the administration of the recombinant IFN subtypes restored DSS-induced colonic inflammation through the upregulation of CD4(+) Treg cells. We identified heterozygous IFNA10 and IFNA4 variants as a cause of impaired function and CD susceptibility genes in Chinese patients from multiple center based study. These findings might provide clues in the understanding of the genetic heterogeneity of CD and lead to better screening and improved treatment.
Assuntos
Doença de Crohn/genética , Exoma/genética , Interferon-alfa/genética , Doença Aguda , Adolescente , Adulto , Animais , Povo Asiático/genética , Sequência de Bases , Antígenos CD4/metabolismo , Estudos de Casos e Controles , Linhagem Celular , Quimiocinas/genética , Quimiocinas/metabolismo , Criança , China , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Doença de Crohn/patologia , Citocinas/genética , Citocinas/metabolismo , Análise Mutacional de DNA , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Hepacivirus/genética , Hepacivirus/fisiologia , Heterozigoto , Humanos , Interferon-alfa/sangue , Interferon-alfa/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Plasmídeos/genética , Plasmídeos/metabolismo , Polimorfismo de Nucleotídeo Único , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Replicação Viral , Adulto JovemRESUMO
The role of Pokemon (POK erythroid myeloid ontogenic actor), a recently identified POK transcription factor with proto-oncogenic activity, in hepatocellular carcinogenesis has only been assessed by a few studies. Our previous study revealed that Pokemon is overexpressed in hepatocellular carcinomas (HCC) and promotes HCC cell proliferation and migration via an AKT- and ERK- dependent manner. In the present study, we used the TUNEL assay and FACS analysis to demonstrate that oxaliplatin induced apoptosis was significantly increased in cells with silenced Pokemon. Western blots showed that p53 expression and phosphorylation were significantly increased in Pokemon defective cells, thereby initiating the mitochondria-mediated and death receptor-mediated apoptotic pathways. In the mitochondria-mediated pathway, expression of pro-apoptotic Bcl-2 family members (including Bad, Bid, Bim and Puma) as well as AIF was increased and decreasing the mitochondrial membrane potential resulted in cytochrome C released from mitochondrial in HepG2 si-Pokemon cells. In addition, upon oxaliplatin treatment of Pokemon-silenced cells, the FAS receptor, FADD and their downstream targets caspase-10 and caspase-8 were activated, causing increased release of caspase-8 active fragments p18 and p10. Increased activated caspase-8-mediated cleavage and activation of downstream effector caspases such as caspase-9 and caspase-3 was observed in HepG2 si-Pokemon cells as compared to control. Therefore, Pokemon might serve as an important mediator of crosstalk between intrinsic and extrinsic apoptotic pathways in HCC cells. Moreover, our findings suggest that Pokemon could be an attractive therapeutic target gene for human cancer therapy.
Assuntos
Apoptose , Carcinoma Hepatocelular/metabolismo , Caspases/metabolismo , Proteínas de Ligação a DNA/genética , Inativação Gênica , Neoplasias Hepáticas/metabolismo , Mitocôndrias Hepáticas/metabolismo , Fatores de Transcrição/genética , Receptor fas/metabolismo , Sequência de Bases , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Primers do DNA , Humanos , Marcação In Situ das Extremidades Cortadas , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologiaRESUMO
Inflammatory bowel disease (IBD) can lead to an increased risk of developing colorectal cancer (CRC). The aim of this study was to establish a model for combined bone marrow transplantation (BMT) and colitis-associated colorectal cancer (CAC) and to define the contribution of BM-derived cells during the inflammation associated with carcinogenesis. We established a model for BMT using green fluorescent protein (GFP) transgenic mice, followed by AOM/DSS-induced CAC, and performed confocal microscopy analysis on in vivo living tissue and frozen tumor sections. Our imaging analyses showed that GFP-positive cells extensively infiltrated the tumor stroma and that some WGA and GFP or CD31 and GFP double-positive cells were observed in the lining of tumor vessels. Flow cytometry analysis of the tumor-infiltrating cells showed that the GFP-positive CD11c+ DCs cells were one-third of the GFP+/CD11C- cells, and that half of these DCs (0.96% vs 1.02%) were GFP-positive BM-derived cells. The majority of CD4(+) T cells were GFP-negative (12.02% vs 1.9%), and we discovered a novel CD4(+) CD11c(+) DC subset (0.34% vs 1.64%). In conclusion, we defined the distribution of BM-derived endothelial cells, CD11c(+) DCs and CD4(+) T cells in tumors. This model might be useful for elucidating the diverse BM-derived cell types and functions during the progression of colitis-associated colorectal cancer.
Assuntos
Células da Medula Óssea/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Colite/metabolismo , Neoplasias Colorretais/metabolismo , Células Dendríticas/metabolismo , Células Endoteliais/metabolismo , Animais , Azoximetano , Transplante de Medula Óssea/métodos , Antígeno CD11c/metabolismo , Linhagem Celular , Colite/induzido quimicamente , Neoplasias Colorretais/induzido quimicamente , Sulfato de Dextrana , Citometria de Fluxo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia Confocal , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismoRESUMO
We aimed to confirm the role of ECHS1 as a binding protein of HBsAg (HBs) and investigate its function during the development of hepatocellular carcinoma (HCC). Our results show that both exogenous and endogenous ECHS1 proteins bind to HBs and co-localize in the cytoplasm in vitro. The coexistence of HBs and ECHS1 enhances HepG2 cell apoptosis, affects ECHS1 localization in the mitochondria and induces apoptosis by decreasing the mitochondrial membrane potential (MMP). These findings suggest that ECHS1 may be applied as a potential therapeutic target during the treatment of HBV-related hepatitis or HCC.