RESUMO
Drosophila is a crucial biological experimental teaching material extensively utilized in experimental teaching. In this experimental teaching, each student typically needs to manually identify hundreds of fruit flies and record multiple of each fly. This task involves substantial workload, and the classification standards can be inconsistent. To address this issue, we introduce a deep convolutional neural network that classifies the traits of every fruit fly, using a two-stage consisting of an object detector and a trait classifier. We propose a keypoint-assisted classification model with tailored training session for the trait classification task and significantly enhanced the model interpretability. Additionally, we've enhanced the RandAugment method to better fit the features of our task. The model is trained with progressive learning and adaptive regularization under limited computational resources. The final classification model, which utilizes MobileNetV3 as backbone, achieves an accuracy of 97.5%, 97.5% and 98% for the eyes, wings, gender tasks, respectively. After optimization, the model is highly lightweight, classifying 600 fruit fly traits from raw images in 10 seconds and having a size less than 5 MB. It can be easily deployed on any android device. The development of this system is conducive to promoting the experimental teaching, such as verifying genetic laws with Drosophila as the research object. It can also be used for scientific research involving a large number of Drosophila classifications, statistics and analyses.
Assuntos
Drosophila , Redes Neurais de Computação , Animais , Drosophila/genética , Computadores , TecnologiaRESUMO
The ABO blood type is one of the most common and widely used genetic traits in humans. Three glycosyltransferase-encoding gene alleles, IA, IB and i, produce three red blood cell surface antigens, by which the ABO blood type is classified. By using the ABO blood type experiment as an ideal case for genetics teaching, we can easily introduce to the students several genetic concepts, including multiple alleles, gene interaction, single nucleotide polymorphism (SNP) and gene evolution. Herein we have innovated and integrated our ABO blood type genetics experiments. First, in the section of Molecular Genetics, a new method of ABO blood genotyping was established: specific primers based on SNP sites were designed to distinguish three alleles through quantitative real-time PCR. Next, the experimental teaching method of Gene Evolution was innovated in the Population Genetics section: a gene-evolution software was developed to simulate the evolutionary tendency of the ABO genotype encoding alleles under diverse conditions. Our reform aims to extend the contents of genetics experiments, to provide additional teaching approaches, and to improve the learning efficiency of our students eventually.
Assuntos
Sistema ABO de Grupos Sanguíneos/genética , Técnicas de Genotipagem/métodos , Alelos , Primers do DNA/genética , Genética Populacional/métodos , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , EstudantesRESUMO
Blood type, which harbors abundant genetics meaning, is one of the most common phenotypes in human life. With the development of science and technology, its significance is unceasingly updated and new finding is increasingly emerging, which constantly attracts people to decipher the heredity mechanism of blood type. In addition to four main associated contents, i.e., Mendelian inheritance, genetic linkage, gene mutations, and chromosome abnormalities, the blood type case also covers many other aspects of the genetics knowledge. Based on the genetic knowledge context, we can interest the students and improve the teaching output in genetic teaching practice by combining with explaining ABO blood type case and heredity mechanism, expanding leucocyte groups, and introducing infrequent blood type such as Bombay blood, Rh and MN. By carrying out the related experimental teaching, we could drive the student to integrate theory with practice. In genetic experimental teaching, 80% of the students chose this optional experiment, molecular identification of ABO blood type, and it greatly interested them. Using appropriate blood type case in teaching related knowledge, organizing PPT exhi-bition and the debating discussion activities, it could provide opportunities for student to propose their own opinions, guide the student to thinking deeply, and develop their abilities to analyze and solve problem. Afterwards, students will gain in-depth comprehension about the fundamental knowledge of genetics.
Assuntos
Conhecimento , Estudantes , Compreensão , Genética/educação , Humanos , Ensino , TecnologiaRESUMO
The α1,3/4-fucosyltransferases (FUT) subfamily are key enzymes in cell surface antigen synthesis during various biological processes. A novel role of FUTs in tumorigenesis has been discovered recently, however, the underlying mechanism remains largely unknown. Here, we characterized FUT6, a member of α1,3/4-FUT subfamily, in human hepatocellular carcinoma (HCC). In HCC tissues, the expression levels of FUT6 and its catalytic product SLe(x) were significantly up-regulated. Overexpression of FUT6 in HCC cells enhanced S-phase cell population, promoted cell growth and colony formation ability. Moreover, subcutaneously injection of FUT6-overexpressing cells in nude mice promoted cell growth in vivo. In addition, elevating FUT6 expression markedly induced intracellular Akt phosphorylation, and suppressed the expression of the cyclin-dependent kinases inhibitor p21. Bath application of the PI3K inhibitor blocked FUT6-induced Akt phosphorylation, p21 suppression and cell proliferation. Our results suggest that FUT6 plays an important role in HCC growth by regulating the PI3K/Akt signaling pathway.
Assuntos
Carcinoma Hepatocelular/patologia , Fucosiltransferases/metabolismo , Neoplasias Hepáticas/patologia , Animais , Carcinoma Hepatocelular/enzimologia , Linhagem Celular Tumoral , Proliferação de Células , Fucosiltransferases/genética , Humanos , Neoplasias Hepáticas/enzimologia , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
ADAM23 (a disintegrin and metalloprotease 23), a member of brain MDC (macrophage-derived chemokine) family, is important for the development of CNS (central nervous system). P19 mouse embryonal carcinoma cells can differentiate into neurons when cultured in aggregates and induced with RA (retinoic acid). We have found that under conditions without RA induction, knocking down ADAM23 with RNAi (RNA interference) promoted neuronal differentiation, and similarly recombinant GST (glutathione transferase)-ADAM23-DIS protein inhibited neuronal differentiation of P19/ADAM23KD (P19/ADAM23-knockdown) cells. In P19/ADAM23KD, there were more cells arrested in G1 phase than normal P19 cells, due to the up-regulation of P57KIP2 and P27KIP1 expression. P27KIP1 was up-regulated during the differentiation process of both P19/ADAM23KD cells without RA induction, and P19 cells with RA induction. Transient overexpression of P27KIP1 in P19 cells also promoted neuronal differentiation of P19 cells. The findings indicate that ADAM23 suppresses neuronal differentiation through its disintegrin domain, and Adam23 KD up-regulates P27KIP1 in P19/ADAM23KD cells, one reason that P19/ADAM23KD cells can differentiate into neurons without RA induction.
Assuntos
Proteínas ADAM/genética , Inibidor de Quinase Dependente de Ciclina p27/genética , Proteínas do Tecido Nervoso/genética , Neurogênese , Neurônios/citologia , Interferência de RNA , Proteínas ADAM/metabolismo , Animais , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Técnicas de Silenciamento de Genes , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Tretinoína/metabolismo , Regulação para CimaRESUMO
Sodium butyrate (NaBu), a histone deacetylase inhibitor, has been shown to inhibit cell growth, induce cell differentiation and apoptosis in multiple cell lines. In present study, we revealed the dual effects of NaBu in regulating hepatocellular carcinoma (HCC) cells. In two different HCC cell lines, SK-Hep1 and SMMC-7721, low concentrations of NaBu induced a significant increase in cell growth ratio and S-phase cell percentage, accompanied by a reduced p21 Cip1 expression at both mRNA and protein levels, while dissimilarly, high concentrations of NaBu inhibited cell growth and induced G1 arrest through up-regulation of p21 Cip1 and p27 Kip1 protein expression. The reduction of p45 Skp2 expression further indicated that the ubiquitin-mediated protein degradation might play a role in NaBu-induced up-regulation of p21 Cip1 and p27 Kip1. Moreover, the high concentration of NaBu was also able to trigger HCC cell apoptosis. Taken together, these results demonstrate the distinct effects of NaBu at different dosages. This finding may contribute to develop more effective tumor therapeutic protocols of NaBu in HCC.
Assuntos
Butiratos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Acetilação/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Butiratos/farmacologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Histonas/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologiaRESUMO
Experimental gene engineering is a laboratory course focusing on the molecular structure, expression pattern and biological function of genes. Providing our students with a solid knowledge base and correct ways to conduct research is very important for high-quality education of genetic engineering. Inspired by recent progresses in this field, we improved the experimental gene engineering course by adding more updated knowledge and technologies and emphasizing on the combination of teaching and research, with the aim of offering our students a good start in their scientific careers.
Assuntos
Clonagem Molecular , Engenharia Genética , Genética/educação , CurrículoRESUMO
Death-associated protein kinase (DAPk) family has emerged as a novel subfamily of pro-apoptotic serine/threonine kinase in the last 10 years. Although the functions of DAPk have been well documented, those of other family members remain uncertain. In this work, we characterized the expression pattern of human DAPk like kinase/Zipper interacting protein kinase (Dlk/ZIP kinase) in cancer specimens and cell lines. Dlk expression level was significantly down-regulated in cervical carcinoma cells compared to the surrounding non-tumorous tissues. Overexpression of Dlk led to cell morphological changes, suppressed colony formation and elevated cell apoptosis in cancer cell lines. Both the kinase activity and the cytoplasmic localization were required for its pro-apoptotic tendency. Mechanism exploration revealed that upon serum deprivation, Dlk overexpression could sensitize cells to apoptosis while overexpression of the kinase inactive mutant (Dlk-K42A) was able to rescue apoptotic cell death. Our data thus implicates that Dlk plays a positive role in modulating death-related signaling pathways. Reconstitution of Dlk expression might bring a potential therapeutic approach to cervical carcinoma treatments.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Apoptose , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Neoplasias/enzimologia , Proteínas Supressoras de Tumor/metabolismo , Linhagem Celular Tumoral , Proteínas Quinases Associadas com Morte Celular , Humanos , Neoplasias/patologiaRESUMO
Textbook construction is an important part of course construction. The development of the Chinese genetics teaching has been full of ups and downs, demonstrating its specificity compared with other subjects of life science. Through the investigation upon the developmental course of genetics textbooks in China from before liberation to the 21st century, we hope that we can provide valuable reference for composing new textbooks that fit the characteristic of undergraduates teaching, and keep close to the genetics front, bringing valuable reference to the cultivation of application and study talents with basic genetics knowledge and innovation ability.
Assuntos
Genética/educação , Materiais de Ensino/normas , Universidades , ChinaRESUMO
Breast cancer metastasis suppressor 1 (BRMS1) is a tumor metastasis suppressor implicated in multiple steps during the metastatic cascade. Many proteins interacting with BRMS1 have been identified to unravel the intracellular signaling mechanisms. In the present study, we report that FANCI is a novel interacting protein of BRMS1 as determined by coimmunoprecipitation assay. The linker region between two coiledcoil motifs of BRMS1 is required for BRMS1FANCI interaction. FANCI is an essential protein in the Fanconi anemia (FA) pathway responsible for the repair of DNA interstrand crosslinks (ICLs). We demonstrated that knockdown or knockout of BRMS1 significantly diminished the monoubiquitination of FANCI and FANCD2 in response to DNA ICL damage. BRMS1deficient cells exhibited suppressed FANCD2 foci formation and hypersensitivity to ICLs. Moreover, rescue assays by utilizing different BRMS1 constructs suggested that BRMS1FANCI interaction is necessary for the regulatory role of BRMS1 in the FA pathway. Overall, our findings characterize BRMS1 as a novel regulatory protein functioning in the DNA repair pathway via protein interaction.
Assuntos
Dano ao DNA/fisiologia , DNA/metabolismo , Proteínas de Grupos de Complementação da Anemia de Fanconi/metabolismo , Proteínas Repressoras/metabolismo , Linhagem Celular , Reparo do DNA/fisiologia , Anemia de Fanconi/metabolismo , Células HEK293 , Humanos , Transdução de Sinais/fisiologia , Ubiquitinação/fisiologiaRESUMO
Zinc finger proteins (ZNFs) are one of the most abundant proteins in eukaryotic genomes with extraordinarily diverse functions. ZNF233 is located on 19q13.31 and encodes a 670-amino acid protein belonging to the Krüppel C2H2-type ZNF family. However, little is known about the role of ZNF233 in cancer progression. In this study, we reported for the first time that ZNF233 mRNA was remarkably up-regulated in hepatocellular carcinoma (HCC) tissues in comparison with corresponding non-tumorous normal liver tissues. ZNF233 expression level was correlated with tumor grade, tumor stage and prognosis of HCC patients. We further investigated the effect of ZNF233 on HCC cell growth. It is found that overexpression of ZNF233 in SMMC-7721 could promote G1/S transition and thus accelerate cell growth ratio. Consistently, knockdown of ZNF233 in QGY-7701 cells successfully suppressed cell proliferation in vitro and in vivo. Further immunohistochemical staining revealed a reduced Ki-67-positive cell percentage in xenografted tumor derived from ZNF233-knocking down cells. Taken together, these results demonstrate a positive role of ZNF233 in regulating HCC cell growth. ZNF233 might be developed as a novel biomarker and a potential therapeutic target for HCC.
Assuntos
Carcinoma Hepatocelular/patologia , Técnicas de Silenciamento de Genes/métodos , Neoplasias Hepáticas/patologia , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Regulação para Cima , Animais , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Masculino , Camundongos , Gradação de Tumores , Transplante de Neoplasias , Prognóstico , Dedos de ZincoRESUMO
Tumor metastasis suppressor factor BRMS1 can regulate the metastasis of breast cancer and other tumors. Here we report scinderin (SCIN) as a novel transcriptional target of BRMS1. SCIN protein belongs to the cytoskeletal gelsolin protein superfamily and its involvement in tumorigenesis remains largely illusive. An inverse correlation between the expression levels of BRMS1 and SCIN was observed in hepatocellular carcinoma (HCC) cells and tissues. On the molecular level, BRMS1 binds to SCIN promoter and exerts a suppressive role in regulating SCIN transcription. FACS analysis and caspase 9 immunoblot reveal that knockdown of SCIN expression can sensitize HCC cells to chemotherapeutic drugs, leading to suppression of tumor growth in vivo. Consistently, overexpression of SCIN protects cells from apoptotic death, contributing to increased xenografted HCC cell growth. In summary, our study reveals SCIN as a functional apoptosis regulator as well as a novel target of BRMS1 during HCC tumorigenesis. Inhibition of SCIN might bring a potential cancer therapy approach.
RESUMO
Breast cancer metastasis suppressor 1 (BRMS1) can specifically regulate tumor metastasis in many cancers. Our previous studies have demonstrated that BRMS1 can promote cell apoptosis through regulating osteopontin (OPN) expression in hepatocellular carcinoma (HCC) cells. However, the transcriptional targets of BRMS1 have not been thoroughly studied. In this study, death-associated protein kinase 1 (DAPK1), a tumor suppressor gene with multiple roles in regulating cell death, was identified as a potential transcriptional target of BRMS1 in the whole genome expression microarray. Quantitative real-time PCR and western blot analysis of HCC cells overexpressing BRMS1 further confirmed the transcriptional regulation relationship between BRMS1 and DAPK1. Moreover, DAPK1 expression was frequently decreased or even lost in HCC tissue samples by comparison with neighboring pathologically normal liver tissue, which was consistent with the decreased BRMS1 expression pattern. To unravel the molecular mechanism of BRMS1 in regulating DAPK1, a series of deletion mutants of DAPK1 promoter was subjected to luciferase assay. The luciferase units of -200 to -80 bp region, with two tandem putative NF-κB binding sites, were specifically enhanced by BRMS1 expression. Site-directed mutants of NF-κB binding sites blocked the transcriptional activation effect. In addition, the binding capability of BRMS1 and the putative NF-κB binding sites were demonstrated in the chromatin immunoprecipitation (ChIP) assay. In conclusion, our study characterized DAPK1 as a novel transcriptional target of BRMS1. Transcriptional activation of DAPK1 might be another important mechanism accounting for the metastasis suppressive activity of BRMS1.
Assuntos
Carcinoma Hepatocelular/genética , Proteínas Quinases Associadas com Morte Celular/genética , Neoplasias Hepáticas/genética , Proteínas Repressoras/genética , Ativação Transcricional/genética , Apoptose/genética , Sítios de Ligação , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Proteínas Quinases Associadas com Morte Celular/biossíntese , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Masculino , NF-kappa B/genética , Metástase Neoplásica , Regiões Promotoras Genéticas , Proteínas Repressoras/biossíntese , Deleção de Sequência , Análise Serial de TecidosRESUMO
Breast cancer metastasis suppressor 1 (BRMS1) is a specific tumor metastasis suppressor implicated in the regulation of chromatin modification and gene transcription. However, the molecular mechanism of BRMS1 remains to be elucidated. Here, we report that DBC1 (deleted in breast cancer 1), is a novel interacting protein of BRMS1. The imperfect leucine zipper motifs of BRMS1 and the N-terminal domain of DBC1 are required for the interaction. DBC1 is identified as an important negative regulator of SIRT1's activity and genotoxic stress response. We demonstrated that BRMS1 is able to interrupt endogenous DBC1-SIRT1 association. Consistently, SIRT1-dependent p53 acetylation under genotoxic stress is also affected by BRMS1. Overall, our results identify BRMS1 as a novel regulator of DBC1-SIRT1 complex and SIRT1-dependent p53 deacetylation.
RESUMO
OBJECTIVE: To develop an efficient non-viral gene delivery system in order to transfer CDKN1B gene efficiently into lung and liver carcinoma cells. METHODS: A recombinant plasmid composed of CDKN1B sequence and EYFP as reporter gene was constructed and identified. The recombinant DNA was then formulated the lipids-polycation-DNA complexes(LPDs) with protamine sulfate. Several kinds of lung and liver carcinoma cells were transfected by means of LPDs. The physicochemical properties of LPDs were investigated using PCS method and TEM, respectively. The expression of EYFP in A549 cells was observed under fluorescent microscope and evaluated by flow cytometry analysis. Finally, the production of CDKN1B protein in transfected LLC, Chang and 7721 cells was identified by Western blot analysis. RESULTS: The average diameter of the LPDs were 167 nm with the polydispersity index of 0.35. The average zeta potential of LPDs was +32.6 mV. LPDs look like a sunken sphere. The fluoresent microscope picture clearly indicated the expression of EYFP in A549 cells. The flow cytometry result showed that the transfection efficiency of LPDs in A549 cells was comparable with that of LipofectAMINE, the positive control. Western blot analysis confirmed the production of CDKN1B protein in LLC, Chang and 7721 cells transfected with LPDs, while no CDKN1B protein was detected in cells transfected with naked DNA. CONCLUSION: The construction of the recombinant plasmid is successful. LPDs can deliver the recombinant plasmid to lung carcinoma cells and liver carcinoma cells with high efficiency. Therefore, this kind of gene delivery system has the potential uses for the treatment of lung and liver cancer.
Assuntos
Inibidor de Quinase Dependente de Ciclina p27/genética , Lipossomos/química , Plasmídeos/genética , Poliaminas/química , Transfecção/métodos , Western Blotting , Linhagem Celular , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Citometria de Fluxo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Plasmídeos/química , Polieletrólitos , Protaminas/químicaRESUMO
A metalloprotease and disintegrin (ADAM) is a family of membrane-anchored proteins and all family members have a multi-domain structure containing a zinc metalloprotease domain and a disintegrin domain that may serve as an integrin ligand. Here we reported two novel mammalian transcripts of Adam23, named Adam23 beta and Adam23 gamma, to be involved in the development and functional activities of mammalian brains. Adam23 gamma was isolated from a 22-week human fetal brain cDNA library, using an EST homologous to Adam as a probe, and is 100% homologous to human Adam23 (Adam23 alpha) except that it lacks a fragment of 91 bp near the C-terminal, thus it could not form obvious transmembrane domain. Adam23 beta was discovered while the diversity at the transmembrane domain (TM) was analyzed. Adam23 beta has a different sequence in the 91 nucleotides and thus encode different transmembrane domain. Adam23 beta and Adam23 gamma are mainly expressed in brain like Adam23 alpha. RT-PCR experiments in mouse brain also detected the two isoforms, consistent with observation of Northern analysis of human RNAs. Furthermore, results of RT-PCR amplification of Adam23 gamma in mouse brains of different developmental stages revealed a developmentally regulated expression pattern: Adam23 gamma is expressed in embryonic and infant brain, and disappeared after the 10th postnatal day. This temporally changing expression pattern of Adam23 gamma suggests that ADAM23 gamma likely plays an important role in brain development.
Assuntos
Encéfalo/metabolismo , Desintegrinas/genética , Regulação da Expressão Gênica no Desenvolvimento , Metaloendopeptidases/genética , Proteínas do Tecido Nervoso/genética , Proteínas ADAM , Animais , Sequência de Bases , Northern Blotting , Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Clonagem Molecular , DNA Complementar/química , DNA Complementar/genética , Éxons/genética , Feminino , Perfilação da Expressão Gênica , Genes/genética , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Isoformas de Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
Breast cancer metastasis suppressor 1 (BRMS1) is able to suppress tumor metastasis without affecting primary tumor growth in various cancers. Here, we report a novel transcript variant of human BRMS1, termed BRMS1.vh. BRMS1.vh is identical to the major BRMS1 variant (BRMS1.v1) except for missing base pairs 683-775, encoding a 215-amino acid protein lacking a functional nuclear localization sequence. Expression of BRMS1.vh in hepatocellular carcinoma (HCC) cells suppressed NF-κB signaling pathway, sensitized cells to apoptotic stimuli, leading to suppressed tumor growth. Taken together, our results suggest a potential role for BRMS1.vh in regulating cell apoptosis and tumor growth in HCC.
Assuntos
Carcinoma Hepatocelular/metabolismo , Clonagem Molecular , Variação Genética , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/metabolismo , Transcrição Gênica , Processamento Alternativo , Sequência de Aminoácidos , Animais , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Genes Reporter , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Dados de Sequência Molecular , NF-kappa B/metabolismo , Proteínas de Neoplasias/genética , Proteínas Repressoras , Transdução de Sinais , Fatores de Tempo , Transfecção , Carga TumoralRESUMO
Breast cancer metastasis suppressor 1 (BRMS1) was originally identified as an active metastasis suppressor in human breast cancer. Loss of BRMS1 expression correlates with tumor progression, and BRMS1 suppresses several steps required for tumor metastasis. However, the role of BRMS1 in hepatocellular carcinoma (HCC) remains elusive. In this study, we found that the expression level of BRMS1 was significantly down-regulated in HCC tissues. Expression of BRMS1 in SK-Hep1 cells did not affect cell growth under normal culture conditions, but sensitized cells to apoptosis induced by serum deprivation or anoikis. Consistently, knockdown of endogenous BRMS1 expression in Hep3B cells suppressed cell apoptosis. We identified that BRMS1 suppresses osteopontin (OPN) expression in HCC cells and that there is a negative correlation between BRMS1 and OPN mRNA expression in HCC tissues. Moreover, knockdown of endogenous OPN expression reversed the anti-apoptosis effect achieved by knockdown of BRMS1. Taken together, our results show that BRMS1 sensitizes HCC cells to apoptosis through suppressing OPN expression, suggesting a potential role of BRMS1 in regulating HCC apoptosis and metastasis.
Assuntos
Apoptose/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Regulação para Baixo , Proteínas de Neoplasias/metabolismo , Osteopontina/genética , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Proteínas de Neoplasias/deficiência , Proteínas de Neoplasias/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas RepressorasRESUMO
INTRODUCTION: Integrins, which are heterodimeric membrane glycoproteins, consist of a family of cell-surface receptors mediating cell-matrix and cell-cell adhesion. Analysis of tumor-associated integrins has revealed an important relationship between integrins and tumor development, bringing new insights into integrin-based cancer therapies. Hepatocellular carcinoma (HCC) is one of the most malignant tumors worldwide and integrins appeal to be a novel group of potential therapeutic targets for HCC. AREAS COVERED: This review summarizes the current knowledge of integrins involved in HCC and the potential of integrin-targeted drugs in HCC therapy. A brief introduction on the structure, biological function and regulatory mechanism of integrins is given. The distinct expression patterns and biological functions of HCC-associated integrins are described. Finally, the current situation of integrin-based therapies in HCC and other tumor types are extensively discussed in the light of their implications in preclinical and clinical trials. EXPERT OPINION: To date, increasing numbers of integrin-targeted drugs are undergoing development and they exhibit diverse effects in cancer clinical trials. Tumor heterogeneity should be emphasized in developing effective integrin-targeted drugs specific for HCC. A better understanding of how integrins cooperatively function in HCC will assist in designing more successful integrin-targeted therapeutic drugs and corresponding approaches.