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1.
Chinese Journal of Lung Cancer ; (12): 692-700, 2023.
Article in Chinese | WPRIM | ID: wpr-1010076

ABSTRACT

With the development of medical technology, tumor vaccines as a novel precise immunotherapy approach have gradually received attention in clinical applications. Against the backdrop of the global corona virus disease 2019 (COVID-19) outbreak, vaccine technology has further advanced. Depending on the types of antigens, tumor vaccines can be divided into whole-cell vaccines, peptide vaccines, messenger ribonucleic acid (mRNA) vaccines, recombinant virus vaccines, etc. Although some tumor vaccines have been marketed and achieved certain therapeutic effects, the results of tumor vaccines in clinical trials have been unsatisfactory in the past period. With the maturation of next-generation sequencing (NGS) technology and the continuous development of bioinformatics, dynamic monitoring of the entire process of tumor subpopulation development has become a reality, which has laid a solid foundation for personalized, neoantigen-centered therapeutic tumor vaccines. This article reviews the recent developments of tumor vaccines of different types, starts with lung cancer and summarizes the achievements of tumor vaccines in clinical applications, and provides an outlook for the future development of antigen-centered tumor vaccines.
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Subject(s)
Humans , Cancer Vaccines/therapeutic use , Antigens, Neoplasm , Lung Neoplasms/drug therapy , Neoplasms/genetics , Computational Biology , Immunotherapy/methods , Lung
2.
Chinese Journal of Biotechnology ; (12): 1374-1389, 2023.
Article in Chinese | WPRIM | ID: wpr-981144

ABSTRACT

Sequestosome 1 (SQSTM1/p62) is a selective autophagy adaptor protein that plays an important role in the clearance of proteins to be degraded as well as in the maintenance of cellular proteostasis. p62 protein has multiple functional domains, which interact with several downstream proteins to precisely regulate multiple signaling pathways, thereby linking p62 to oxidative defense systems, inflammatory responses and nutrient sensing. Studies have shown that mutation or abnormal expression of p62 is closely related to the occurrence and development of various diseases, including neurodegenerative diseases, tumors, infectious diseases, genetic diseases and chronic diseases. This review summarizes the structural features and molecular functions of p62. Moreover, we systematically introduce its multiple functions in protein homeostasis and regulation of signaling pathways. Furthermore, the complexity and versatility of p62 in the occurrence and development of diseases are summarized, with the aim to provide a reference for understanding the function of p62 protein and facilitating related disease research.


Subject(s)
Humans , Autophagy/genetics , Sequestosome-1 Protein/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Signal Transduction , Neoplasms/genetics
3.
Acta Physiologica Sinica ; (6): 269-278, 2023.
Article in Chinese | WPRIM | ID: wpr-981004

ABSTRACT

DMRT, a gene family related to sexual determination, encodes a large group of transcription factors (DMRTs) with the double-sex and mab-3 (DM) domain (except for DMRT8), which is able to bind to and regulate DNAs. Current studies have shown that the DMRT gene family plays a critical role in the development of sexual organs (such as gender differentiation, gonadal development, germ cell development, etc.) as well as extrasexual organs (such as musculocartilage development, nervous system development, etc.). Additionally, it has been suggested that DMRTs may be involved in the cancer development and progression (such as prostate cancer, breast cancer, lung cancer, etc.). This review summarizes the research progress about the mammalian DMRTs' structure, function and its critical role in cancer development, progression and therapy (mainly in human and mice), which suggests that DMRT gene could be a candidate gene in the study of tumor formation and therapeutic strategy.


Subject(s)
Male , Animals , Humans , Mice , Transcription Factors/genetics , Mammals/metabolism , Cell Differentiation , Neoplasms/genetics
4.
Chinese Medical Journal ; (24): 757-766, 2023.
Article in English | WPRIM | ID: wpr-980874

ABSTRACT

Long non-coding RNAs (lncRNAs) reportedly function as important modulators of gene regulation and malignant processes in the development of human cancers. The lncRNA JPX is a novel molecular switch for X chromosome inactivation and differentially expressed JPX has exhibited certain clinical correlations in several cancers. Notably, JPX participates in cancer growth, metastasis, and chemoresistance, by acting as a competing endogenous RNA for microRNA, interacting with proteins, and regulating some specific signaling pathways. Moreover, JPX may serve as a potential biomarker and therapeutic target for the diagnosis, prognosis, and treatment of cancer. The present article summarizes our current understanding of the structure, expression, and function of JPX in malignant cancer processes and discusses its molecular mechanisms and potential applications in cancer biology and medicine.


Subject(s)
Humans , RNA, Long Noncoding/genetics , Neoplasms/genetics , MicroRNAs/genetics , Gene Expression Regulation , X Chromosome Inactivation
5.
Chinese Medical Journal ; (24): 2086-2100, 2023.
Article in English | WPRIM | ID: wpr-1007627

ABSTRACT

BACKGROUND@#Metastasis is the main cause of tumor-associated death and mainly responsible for treatment failure of breast cancer. Autophagy accelerates tumor metastasis. In our work, we aimed to investigate the possibility of microRNAs (miRNAs) which participate in the regulation of autophagy to inhibit tumor metastasis.@*METHODS@#MiRNA array and comprehensive analysis were performed to identify miRNAs which participated in the regulation of autophagy to inhibit tumor metastasis. The expression levels of miR-3653 in breast cancer tissues and cells were detected by quantitative real-time polymerase chain reaction. In vivo and in vitro assays were conducted to determine the function of miR-3653. The target genes of miR-3653 were detected by a dual luciferase reporter activity assay and Western blot. The relationship between miR-3653 and epithelial-mesenchymal transition (EMT) was assessed by Western blot. Student's t -test was used to analyze the difference between any two groups, and the difference among multiple groups was analyzed with one-way analysis of variance and a Bonferroni post hoc test.@*RESULTS@#miR-3653 was downregulated in breast cancer cells with high metastatic ability, and high expression of miR-3653 blocked autophagic flux in breast cancer cells. Clinically, low expression of miR-3653 in breast cancer tissues (0.054 ± 0.013 vs . 0.131 ± 0.028, t  = 2.475, P  = 0.014) was positively correlated with lymph node metastasis (0.015 ± 0.004 vs . 0.078 ± 0.020, t  = 2.319, P  = 0.023) and poor prognosis ( P  < 0.001). miR-3653 ameliorated the malignant phenotypes of breast cancer cells, including proliferation, migration (MDA-MB-231: 0.353 ± 0.013 vs . 1.000 ± 0.038, t  = 16.290, P  < 0.001; MDA-MB-468: 0.200 ± 0.014 vs . 1.000 ± 0.043, t  = 17.530, P  < 0.001), invasion (MDA-MB-231: 0.723 ± 0.056 vs . 1.000 ± 0.035, t  = 4.223, P  = 0.013; MDA-MB-468: 0.222 ± 0.016 vs . 1.000 ± 0.019, t  = 31.050, P  < 0.001), and colony formation (MDA-MB-231: 0.472 ± 0.022 vs . 1.000 ± 0.022, t  = 16.620, P  < 0.001; MDA-MB-468: 0.650 ± 0.040 vs . 1.000 ± 0.098, t  = 3.297, P  = 0.030). The autophagy-associated genes autophagy-related gene 12 ( ATG12 ) and activating molecule in beclin 1-regulated autophagy protein 1 ( AMBRA1 ) are target genes of miR-3653. Further studies showed that miR-3653 inhibited EMT by targeting ATG12 and AMBRA1 .@*CONCLUSIONS@#Our findings suggested that miR-3653 inhibits the autophagy process by targeting ATG12 and AMBRA1 , thereby inhibiting EMT, and provided a new idea and target for the metastasis of breast cancer.


Subject(s)
Cell Line, Tumor , Epithelial-Mesenchymal Transition/genetics , MicroRNAs/metabolism , Autophagy/genetics , Genes, Regulator , Gene Expression Regulation, Neoplastic/genetics , Cell Proliferation/genetics , Cell Movement/genetics , Neoplasms/genetics
6.
Chinese Medical Journal ; (24): 1783-1793, 2023.
Article in English | WPRIM | ID: wpr-1007598

ABSTRACT

Organoids are three-dimensional cellular structures with self-organizing and self-differentiation capacities. They faithfully recapitulate structures and functions of in vivo organs as represented by functionality and microstructural definitions. Heterogeneity in in vitro disease modeling is one of the main reasons for anti-cancer therapy failures. Establishing a powerful model to represent tumor heterogeneity is crucial for elucidating tumor biology and developing effective therapeutic strategies. Tumor organoids can retain the original tumor heterogeneity and are commonly used to mimic the cancer microenvironment when co-cultured with fibroblasts and immune cells; therefore, considerable effort has been made recently to promote the use of this new technology from basic research to clinical studies in tumors. In combination with gene editing technology and microfluidic chip systems, engineered tumor organoids show promising abilities to recapitulate tumorigenesis and metastasis. In many studies, the responses of tumor organoids to various drugs have shown a positive correlation with patient responses. Owing to these consistent responses and personalized characteristics with patient data, tumor organoids show excellent potential for preclinical research. Here, we summarize the properties of different tumor models and review their current state and progress in tumor organoids. We further discuss the substantial challenges and prospects in the rapidly developing tumor organoid field.


Subject(s)
Humans , Neoplasms/genetics , Organoids/pathology , Carcinogenesis , Models, Biological , Precision Medicine/methods , Tumor Microenvironment
7.
Chinese Medical Journal ; (24): 127-137, 2023.
Article in English | WPRIM | ID: wpr-970062

ABSTRACT

Adoptive therapeutic immune cells, such as chimeric antigen receptor (CAR)-T cells and natural killer cells, have established a new generation of precision medicine based on which dramatic breakthroughs have been achieved in intractable lymphoma treatments. Currently, well-explored approaches focus on autologous cells due to their low immunogenicity, but they are highly restricted by the high costs, time consumption of processing, and the insufficiency of primary cells in some patients. Induced pluripotent stem cells (iPSCs) are cell sources that can theoretically produce indefinite well-differentiated immune cells. Based on the above facts, it may be reasonable to combine the iPSC technology and the CAR design to produce a series of highly controllable and economical "live" drugs. Manufacturing hypoimmunogenic iPSCs by inactivation or over-expression at the genetic level and then arming the derived cells with CAR have emerged as a form of "off-the-shelf" strategy to eliminate tumor cells efficiently and safely in a broader range of patients. This review describes the reasonability, feasibility, superiority, and drawbacks of such approaches, summarizes the current practices and relevant research progress, and provides insights into the possible new paths for personalized cell-based therapies.


Subject(s)
Humans , Receptors, Chimeric Antigen/genetics , Induced Pluripotent Stem Cells , Killer Cells, Natural , Cell- and Tissue-Based Therapy , T-Lymphocytes , Immunotherapy, Adoptive , Neoplasms/genetics
8.
Chinese Journal of Epidemiology ; (12): 521-528, 2023.
Article in Chinese | WPRIM | ID: wpr-985522

ABSTRACT

Identifying risk factors of the disease are one of the main tasks of epidemiology. With the advancement of omics technologies (e.g., genome, transcriptome, proteome, metabolome, and exposome), cancer etiology research has entered the stage of systems epidemiology. Genomic research identifies cancer susceptibility loci and uncovers their biological mechanisms. Exposomic research investigates the impact of environmental factors on biological processes and disease risks. The metabolome is downstream of biological regulatory networks, reflecting the effects of the gene, environment, and their interactions, which can help elucidate the biological mechanisms of genetic and environmental risk factors and identify new biomarkers. Here, we reviewed the applications of genomic, exposomic, and metabolomic studies in the etiologic research on cancer. We summarized the importance of multi-omics approaches and systems epidemiology in cancer etiology research and outlined future perspectives.


Subject(s)
Humans , Multiomics , Genomics , Metabolomics , Neoplasms/genetics , Biomarkers
9.
Journal of Zhejiang University. Medical sciences ; (6): 429-438, 2023.
Article in English | WPRIM | ID: wpr-1009905

ABSTRACT

Tumor-derived exosomes play an important role in the tumor micro-environment. The exosome-derived non-coding RNAs are transmitted in the tumor microenvironment in three ways, communication between tumor cells, normal cells affecting tumor cells, and tumor cells affecting normal cells. Through these three ways, exosomal non-coding RNAs are involved in the regulation of tumor progression, affecting tumor angiogenesis, tumor invasiveness, drug resistance, stemness, tumor metabolic repro-gramming and immune escape, resulting in dual roles in promoting or inhibiting tumor development. Exosomes have a membranous structure and their contents are resistant to degradation by extracellular proteases and remain highly stable in body fluids, thus exosome-derived non-coding RNAs are expected to serve as diagnostic and prognostic indicators for a variety of cancers. In addition, exosomes can be used to deliver non-coding RNAs for targeted therapy, or to knock down or modify tumor-promoting non-coding RNAs for tumor therapy. This article reviews the function and communication mechanism of exosomal non-coding RNAs in the tumor microenvironment, including their pathways of action, effects, potential values for tumor biomarkers and treatment targets. This article also points out the issues that need to be further studied in order to promote the progress of extracellular non-coding RNAs in cancer research and their application in tumor diagnosis and treatment.


Subject(s)
Humans , Exosomes , Neoplasms/genetics , Biomarkers, Tumor , Body Fluids , RNA, Untranslated/genetics , Tumor Microenvironment
10.
China Journal of Chinese Materia Medica ; (24): 1421-1430, 2023.
Article in Chinese | WPRIM | ID: wpr-970613

ABSTRACT

Genome-guided oncology refers to a new treatment concept that transcends histological classification and pathological ty-ping and uses drugs according to the genetic characteristics of tumors. New drug development technology and clinical trial design based on this concept provide new ideas for the clinical application of precision oncology. The multi-component and multi-target characteristics of Chinese medicine provide rich resources for the development of tumor-targeting drugs from natural products, and the design of the master protocol trial aiming at the characteristics of precision oncology supports the rapid clinical screening of effective tumor-targeting drugs. The emergence of the synthetic lethality strategy breaks through the bottleneck that the drug can only target the oncogene but cannot do anything to the tumor suppressor gene with the loss-of-function mutation in the past. With the rapid development of high-throughput sequencing technology, the cost of sequencing is also decreasing. For the development of tumor-targeting drugs, how to keep up with the update speed of target information is a difficult problem of concern. Based on the integration of innovative ideas and me-thods of precision oncology, network pharmacology, and synthetic lethality strategy on synthetic lethal interaction network of antitumor Chinese medicine compatibility formula design, and the combination of improvement of innovative clinical trial methods, such as master protocol trial, basket trial, and umbrella trial, unique advantages of Chinese medicine are expected to be exerted beyond the antibody-based drugs and small molecule-based drugs and corresponding targeted drugs are potentially developed for clinical application.


Subject(s)
Humans , Neoplasms/genetics , Medicine, Chinese Traditional , Precision Medicine/methods , Medical Oncology , Antineoplastic Agents/therapeutic use
11.
China Journal of Chinese Materia Medica ; (24): 1330-1342, 2023.
Article in Chinese | WPRIM | ID: wpr-970604

ABSTRACT

This study aimed to explore the mechanism of Cistanches Herba in the treatment of cancer-induced fatigue(CRF) by network pharmacology combined with in vivo and in vitro experiments to provide a theoretical basis for the clinical medication. The chemical constituents and targets of Cistanches Herba were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of CRF were screened out by GeneCards and NCBI. The common targets of traditional Chinese medicine and disease were selected to construct a protein-protein interaction(PPI) network, followed by Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. A visual signal pathway rela-ted to Chinese medicine and disease targets was constructed. The CRF model was induced by paclitaxel(PTX) in mice. Mice were divided into a control group, a PTX model group, and low-and high-dose Cistanches Herba extract groups(250 and 500 mg·kg~(-1)). The anti-CRF effect in mice was evaluated by open field test, tail suspension test, and exhaustive swimming time, and the pathological morphology of skeletal muscle was evaluated by hematoxylin-eosin(HE) staining. The cancer cachexia model in C2C12 muscle cells was induced by C26 co-culture, and the cells were divided into a control group, a conditioned medium model group, and low-, medium-, and high-dose Cistanches Herba extract groups(62.5, 125, and 250 μg·mL~(-1)). The reactive oxygen species(ROS) content in each group was detected by flow cytometry, and the intracellular mitochondrial status was evaluated by transmission electron microscopy. The protein expression levels of hypoxia-inducible factor-1α(HIF-1α), BNIP3L, and Beclin-1 were detected by Western blot. Six effective constituents were screened out from Cistanches Herba. The core genes of Cistanches Herba in treating CRF were AKT1, IL-6, VEGFA, CASP3, JUN, EGFR, MYC, EGF, MAPK1, PTGS2, MMP9, IL-1B, FOS, and IL10, and the pathways related to CRF were AGE-RAGE and HIF-1α. Through GO enrichment analysis, it was found that the main biological functions involved were lipid peroxidation, nutrient deficiency, chemical stress, oxidative stress, oxygen content, and other biological processes. The results of the in vivo experiment showed that Cistanches Herba extract could significantly improve skeletal muscle atrophy in mice to relieve CRF. The in vitro experiment showed that Cistanches Herba extract could significantly reduce the content of intracellular ROS, the percentage of mitochondrial fragmentation, and the protein expression of Beclin-1 and increase the number of autophagosomes and the protein expression of HIF-1α and BNIP3L. Cistanches Herba showed a good anti-CRF effect, and its mechanism may be related to the key target proteins in the HIF-1α signaling pathway.


Subject(s)
Animals , Mice , Cistanche , Network Pharmacology , Beclin-1 , Reactive Oxygen Species , Plant Extracts , Drugs, Chinese Herbal/pharmacology , Molecular Docking Simulation , Medicine, Chinese Traditional , Neoplasms/genetics
12.
Journal of Zhejiang University. Science. B ; (12): 15-31, 2023.
Article in English | WPRIM | ID: wpr-971466

ABSTRACT

Long non-coding RNAs (lncRNAs) play a significant role in maintaining tissue morphology and functions, and their precise regulatory effectiveness is closely related to expression patterns. However, the spatial expression patterns of lncRNAs in humans are poorly characterized. Here, we constructed five comprehensive transcriptomic atlases of human lncRNAs covering thousands of major tissue samples in normal and disease states. The lncRNA transcriptomes exhibited high consistency within the same tissues across resources, and even higher complexity in specialized tissues. Tissue-elevated (TE) lncRNAs were identified in each resource and robust TE lncRNAs were refined by integrative analysis. We detected 1 to 4684 robust TE lncRNAs across tissues; the highest number was in testis tissue, followed by brain tissue. Functional analyses of TE lncRNAs indicated important roles in corresponding tissue-related pathways. Moreover, we found that the expression features of robust TE lncRNAs made them be effective biomarkers to distinguish tissues; TE lncRNAs also tended to be associated with cancer, and exhibited differential expression or were correlated with patient survival. In summary, spatial classification of lncRNAs is the starting point for elucidating the function of lncRNAs in both maintenance of tissue morphology and progress of tissue-constricted diseases.


Subject(s)
Humans , Gene Expression Profiling , Neoplasms/genetics , Organ Specificity , RNA, Long Noncoding/genetics , Transcriptome
13.
Journal of Southern Medical University ; (12): 448-456, 2022.
Article in Chinese | WPRIM | ID: wpr-936337

ABSTRACT

RNA binding protein (RBP) plays a key role in gene regulation and participate in RNA translation, modification, splicing, transport and other important biological processes. Studies have shown that abnormal expression of RBP is associated with a variety of diseases. The Musashi (Msi) family of mammals is an evolutionarily conserved and powerful RBP, whose members Msi1 and Msi2 play important roles in the regulation of stem cell activity and tumor development. The Msi family members regulate a variety of biological processes by binding and regulating mRNA translation, stability and downstream cell signaling pathways, and among them, Msi2 is closely related to embryonic growth and development, maintenance of tumor stem cells and development of hematological tumors. Accumulating evidence has shown that Msi2 also plays a crucial role in the development of solid tumors, mainly by affecting the proliferation, invasion, metastasis and drug resistance of tumors, involving Wnt/β-catenin, TGF-β/SMAD3, Akt/mTOR, JAK/STAT, Numb and their related signaling pathways (Notch, p53, and Hedgehog pathway). Preclinical studies of Msi2 gene as a therapeutic target for tumor have achieved preliminary results. This review summarizes the molecular structure, physiological function, role of Msi2 in the development and progression of various solid tumors and the signaling pathways involved.


Subject(s)
Animals , Hedgehog Proteins , Mammals/metabolism , Neoplasms/genetics , Neoplastic Stem Cells , RNA-Binding Proteins/metabolism , Signal Transduction
14.
Journal of Zhejiang University. Medical sciences ; (6): 1-16, 2021.
Article in English | WPRIM | ID: wpr-879956

ABSTRACT

Epigenetics concerns gene regulatory mechanisms beyond DNA sequence,such as DNA methylation,histone modification,chromatin remodeling,and non-coding RNA. Epigenetic mechanisms play a key role in development,cell fate decision and tumorigenesis. Chromatin modifications and its high order structure across our genome are major forms of epigenetic information,and its establishment and maintenance are closely related to cell metabolism. Metabolic changes in cancer cells include aerobic glycolysis,increased glucose uptake,abnormally active glutamine metabolism,and the use of non-conventional energy supply. These changes meet the vigorous energy and matter needs for the development and spread of cancer,and help tumor cells adapt to hypoxia microenvironment for their survival,proliferation,invasion and migration. There is a complex relationship between epigenetic modifications and cell metabolism in tumor. On the one hand,metabolites in tumor cells may act as cofactors,modification donors or antagonists of epigenetic enzymes,thus modulating the epigenetic landscape. On the other hand,epigenetic modifications can directly regulate the expression of metabolic enzymes,transporters,signaling pathway and transcription factors to affect cell metabolism. This article reviews the crosstalk between epigenetics and cancer metabolism,to explore their potential future applications in the treatment of tumors.


Subject(s)
Humans , Carcinogenesis , DNA Methylation , Epigenesis, Genetic , Gene Expression Regulation , Neoplasms/genetics , Tumor Microenvironment
15.
Journal of Zhejiang University. Medical sciences ; (6): 17-22, 2021.
Article in English | WPRIM | ID: wpr-879949

ABSTRACT

The gene is frequently mutated and abnormally activated in many cancers,and plays an important role in cancer development. Metabolic reprogramming occurs in malignant tumors,which can be one of the key targets for anti-tumor therapy. gene can regulate lipid metabolism through AKT-mTORC1 single axis or multiple pathways,such as lipid synthesis pathways and degradation pathways. Similarly,lipid metabolism can also modify and activate RAS protein and its downstream signaling pathways. This article overviews the current research progress on the interaction between lipid metabolism and ,to provide insight in therapeutic strategies of lipid metabolism for -driven tumors.


Subject(s)
Humans , Genes, ras , Lipid Metabolism/genetics , Neoplasms/genetics , Signal Transduction , ras Proteins/metabolism
16.
Chinese Journal of Biotechnology ; (12): 4111-4123, 2021.
Article in Chinese | WPRIM | ID: wpr-921492

ABSTRACT

In case/control gene expression data, differential expression (DE) represents changes in gene expression levels across various biological conditions, whereas differential co-expression (DC) represents an alteration of correlation coefficients between gene pairs. Both DC and DE genes have been studied extensively in human diseases. However, effective approaches for integrating DC-DE analyses are lacking. Here, we report a novel analytical framework named DC&DEmodule for integrating DC and DE analyses and combining information from multiple case/control expression datasets to identify disease-related gene co-expression modules. This includes activated modules (gaining co-expression and up-regulated in disease) and dysfunctional modules (losing co-expression and down-regulated in disease). By applying this framework to microarray data associated with liver, gastric and colon cancer, we identified two, five and two activated modules and five, five and one dysfunctional module(s), respectively. Compared with the other methods, pathway enrichment analysis demonstrated the superior sensitivity of our method in detecting both known cancer-related pathways and those not previously reported. Moreover, we identified 17, 69, and 11 module hub genes that were activated in three cancers, which included 53 known and three novel cancer prognostic markers. Random forest classifiers trained by the hub genes showed an average of 93% accuracy in differentiating tumor and adjacent normal samples in the TCGA and GEO database. Comparison of the three cancers provided new insights into common and tissue-specific cancer mechanisms. A series of evaluations demonstrated the framework is capable of integrating the rapidly accumulated expression data and facilitating the discovery of dysregulated processes.


Subject(s)
Humans , Gene Expression Profiling , Gene Regulatory Networks , Microarray Analysis , Neoplasms/genetics
17.
China Journal of Chinese Materia Medica ; (24): 24-32, 2021.
Article in Chinese | WPRIM | ID: wpr-878906

ABSTRACT

Nrf2 is the key transcription factor mainly for regulating oxidative homeostasis and cytoprotective responses against oxidative stress. Nrf2/Keap1 pathway is one of the most important cellular defense mechanisms against endogenous or exogenous oxidative stress. With its activation, a wide range of stress-related genes is transactivated to restore the cellular homeostasis. Recent studies revealed that the aberrant activation of Nrf2 is related to the malignant progression, chemotherapeutic drug resistance and poor prognosis. Nrf2 plays a crucial role in cancer malignancy and chemotherapeutic resistance by controlling the intracellular redox homeostasis through the activation of cytoprotective antioxidant genes. Nrf2 inhibitor containing many natural products has been deemed as a novel therapeutic strategy for human malignancies. This article reviews the progress of studies of the Nrf2/Keap1 pathway, and its biological impact in solid malignancies and molecular mechanisms for causing Nrf2 hyperactivation in cancer cells. In conclusion, we summarized the deve-lopment of Nrf2 inhibitors in recent years, in the expectation of providing reference for further drug development and clinical studies.


Subject(s)
Humans , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , Neoplasms/genetics , Oxidation-Reduction , Oxidative Stress
19.
Einstein (Säo Paulo) ; 19: eRB5996, 2021. tab, graf
Article in English | LILACS | ID: biblio-1286282

ABSTRACT

ABSTRACT MicroRNAs are small RNA molecules that regulate gene expression in cells. These small molecules comprise 17 to 25 nucleotides and are able to recognize target messenger RNAs by sequence complementarity and regulate their protein translation. Different microRNAs are expressed in all human cells. There is over 2,500 microRNAs described in humans that are involved in virtually all biological processes. Given their role as gene expression regulators, these molecules have been widely investigated and are thought to be associated with some specific physiological and pathological conditions, being proposed as biomarkers. It has recently been reported that microRNAs are secreted outside cells and are involved in intercellular communication. MicroRNAs in biological fluids are named circulating and have been detected in all body fluids, although the expression profile is specific for each type. The major advantages of using circulating microRNAs as biological markers are the high stability of those molecules and the wide availability of samples. Also, given the individual nature of microRNA expression changes, these molecules have a high potential for use in personalized medicine. In fact, microRNA expression profile determination may support disease recognition and diagnosis, and can be used to monitor therapeutic responses and establish patient prognosis, assisting in choice of treatment. This review provides a general overview of microRNAs and discusses the importance of those molecules in cancer, for deeper understanding of their role in this disease.


RESUMO Os microRNAs são pequenas moléculas de RNAs que regulam a expressão gênica das células. Com entre 17 e 25 nucleotídeos, essas pequenas moléculas reconhecem RNA mensageiro-alvo, por meio da complementariedade entre as sequências, e regulam sua tradução proteica. Todas as células humanas expressam diversos microRNAs. De fato, existem mais de 2.500 microRNAs descritos em humanos, relacionados com praticamente todos os processos biológicos. Devido ao seu papel como reguladores da expressão gênica, essas moléculas têm sido estudadas e relacionadas com algumas condições fisiológicas e patológicas específicas, sendo propostas como biomarcadores. Recentemente, foi descoberto que os microRNAs são normalmente liberados para fora da célula, onde participam da comunicação intercelular. MicroRNAs presentes nos fluidos biológicos são chamados de circulantes e têm sido encontrados em todos os fluidos corporais, porém o perfil de expressão é específico para cada tipo. O uso de microRNAs circulantes como marcadores biológicos apresenta vantagens relacionadas com a alta estabilidade dessas moléculas e a facilidade de obtenção de amostra. Adicionalmente, considerando que as alterações em microRNAs são dependentes das condições individuais, essas moléculas apresentam alto potencial de uso na medicina personalizada. De fato, a determinação do perfil de expressão de microRNAs pode auxiliar na identificação e diagnóstico de doenças, no monitoramento de respostas terapêuticas e na definição do prognóstico dos pacientes, auxiliando na escolha do tratamento. Nesta revisão são apresentados aspectos gerais dos microRNAs, e discute-se a importância dessas moléculas no câncer, visando a uma melhor compreensão de seu papel nessa doença.


Subject(s)
Humans , MicroRNAs/genetics , Neoplasms/genetics , Prognosis , Biomarkers , Gene Expression
20.
Journal of Peking University(Health Sciences) ; (6): 602-607, 2021.
Article in Chinese | WPRIM | ID: wpr-942225

ABSTRACT

OBJECTIVE@#To screen potential pan-cancer biomarkers based on The Cancer Genome Atlas (TCGA) database, and to provide help for the diagnosis and prognosis assessment of a variety of cancers.@*METHODS@#"GDC Data Transfer Tool" and "GDCRNATools" packages were used to obtain TCGA database. After data sorting, a total of 13 cancers were selected for further analysis. False disco-very rate (FDR) < 0.05 and fold change (FC) >1.5 were used as the differential expression criteria to screen genes and miRNAs that were up- or down-regulated in all the 13 cancers. In the receiver operating characteristic curve (ROC curve), the area under the curve (AUC), the best cut-off value and the corresponding sensitivity and specificity were used to reflect diagnostic significance. The Kaplan-Meier method was used to calculate the survival probability and then the log-rank test was performed. Hazard ratio (HR) was calculated to reflect prognostic evaluation significance. DAVID tool were used to perform GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis for differentially expressed genes. STRING and TargetScan tools were used to analyze the regulatory network of differentially expressed genes and miRNAs.@*RESULTS@#A total of 48 genes and 2 miRNAs were differentially expressed in all the 13 cancers. Among them, 25 genes were up-regulated, 23 genes and 2 miRNAs were down-regulated. Most differentially expressed genes and miRNAs had good ability to distinguish between the cases and controls, with AUC, sensitivity and specificity up to 0.8-0.9. Survival analysis results show that differentially expressed genes and miRNAs were significantly associated with patient survival in a variety of cancers. Most up-regulated genes were risk factors for patient survival (HR>1), while most down-regulated genes were protective factors for patient survival (0 < HR < 1). The enrichment analysis of GO and KEGG showed that the differentially expressed genes were mostly enriched in biological events related to cell proliferation. In the regulatory network analysis, a total of 13 differentially expressed genes and 2 differentially expressed miRNAs had regulatory and interaction relationships.@*CONCLUSION@#The 48 genes and 2 miRNAs that were differentially expressed in 13 cancers may serve as potential pan-cancer biomarkers, providing help for the diagnosis and prognosis evaluation of a variety of cancers, and providing clues for the development of broad-spectrum tumor therapeutic targets.


Subject(s)
Humans , Biomarkers, Tumor/genetics , Early Detection of Cancer , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Neoplasms/genetics , Prognosis
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