The Ras/MAPK signaling cascade plays an essential role in the regulation of cellular processes,including proliferation,differentiation,and survival,serving as a pivotal intracellular communication network.Dysregulatio...The Ras/MAPK signaling cascade plays an essential role in the regulation of cellular processes,including proliferation,differentiation,and survival,serving as a pivotal intracellular communication network.Dysregulation of this pathway,frequently attributable to mutations within Ras genes,has been strongly associated with the development of a spectrum of cancers.This review underscores the pivotal role of the Ras/MAPK pathway in oncogenic transformation and tumor progression,briefing the intricate mechanisms through which the aberrant activation of this pathway leads to unbridled cell proliferation,inhibition of apoptosis,promotion of metastasis,and induction of angiogenesis,thereby providing valuable insights into the pathogenesis of malignancies.It also underscores the significance of the Ras/MAPK pathway as a therapeutic target and discusses the challenges and potential of targeted therapies,including combination treatments and personalized medicine approaches,to overcome resistance and enhance treatment efficacy in cancers driven by pathway dysregulation.展开更多
Epstein-Barr virus(EBV)-associated gastric cancer(EBVaGC)cells originate from a single-cell clone infected with EBV.However,more than 95%of patients with gastric cancer have a history of Helicobacter pylori(H.pylori)i...Epstein-Barr virus(EBV)-associated gastric cancer(EBVaGC)cells originate from a single-cell clone infected with EBV.However,more than 95%of patients with gastric cancer have a history of Helicobacter pylori(H.pylori)infection,and H.pylori is a major causative agent of gastric cancer.Therefore,it has long been argued that H.pylori infection may affect the development of EBVaGC,a subtype of gastric cancer.Atrophic gastrointestinal inflammation,a symptom of H.pylori infection,is observed in the gastric mucosa of EBVaGC.Therefore,it remains unclear whether H.pylori infection is a cofactor for gastric carcinogenesis caused by EBV infection or whether H.pylori and EBV infections act independently on gastric cancer formation.It has been reported that EBV infection assists in the oncogenesis of gastric cancer caused by H.pylori infection.In contrast,several studies have reported that H.pylori infection accelerates tumorigenesis initiated by EBV infection.By reviewing both clinical epidemiological and experimental data,we reorganized the role of H.pylori and EBV infections in gastric cancer formation.展开更多
The role that free radicals in general and oxygen radicals in particular play in carcinogenesis has attracted considerable attention in recent years. The oxygen radicals are undesirable but inevitable products of aero...The role that free radicals in general and oxygen radicals in particular play in carcinogenesis has attracted considerable attention in recent years. The oxygen radicals are undesirable but inevitable products of aerobic metabolism in the normal living cell. The cellular antioxidant defense system maintains an appropriate balance between necessary oxidative events and those that are excessive. When this critical balance cannot be maintained because of the overloading of the cellularredox system, oxygen radicals can induce cell damage. They can influence carcinogenesis by inducing DN A damage from direct oxidation or indirectly from DNA-binding products of lipid peroxidation. Oxygen radicals can induce conformational changes in the plasma membrane by lipid peroxidation and protein degradation, thus influencing membrane-associated cellular activities. They are capable of affecting membrane-bound protein kinases, growth factors and their receptors, and, therefore, signal transduction and oncogene activation. Thus, the oxygen radicals can have a major influence on oncogenes and oncogenesis. (C)1990 Academic Press.Inc.展开更多
Pancreatic cancer is a lethal malignancy,whose precursor lesions are pancreatic intraepithelial neoplasm,intraductal papillary mucinous neoplasm,intraductal tubulopapillary neoplasm,and mucinous cystic neoplasm.To bet...Pancreatic cancer is a lethal malignancy,whose precursor lesions are pancreatic intraepithelial neoplasm,intraductal papillary mucinous neoplasm,intraductal tubulopapillary neoplasm,and mucinous cystic neoplasm.To better understand the biology of pancreatic cancer,it is fundamental to know its precursors and to study the mechanisms of carcinogenesis.Each of these precursors displays peculiar histological features,as well as specific molecular alterations.Starting from such pre-invasive lesions,this review aims at summarizing the most important aspects of carcinogenesis of pancreatic cancer,with a specific focus on the recent advances and the future perspectives of the research on this lethal tumor type.展开更多
Colorectal cancer(CRC)poses a severe global health challenge with high incidence and mortality rates.USP37 has been identified as the bona fide deubiquitinase of SND1,playing a critical role in stabilizing SND1,thereb...Colorectal cancer(CRC)poses a severe global health challenge with high incidence and mortality rates.USP37 has been identified as the bona fide deubiquitinase of SND1,playing a critical role in stabilizing SND1,thereby augmenting its oncogenic potential.The interaction between USP37 and SND1 was confirmed through extensive proteomics,ubiquitinomics,and interactomics,underscoring their synergistic effects on CRC proliferation and metastasis.Additionally,CDK1 has emerged as a pivotal regulator of USP37,phosphorylating it at threonine 631 rather than serine 628,enhancing its deubiquitinase activity,and consequently stabilizing SND1 to drive CRC malignancy further.Histological analyses of human CRC samples linked the upregulation of CDK1 and USP37 with increased SND1 levels and poor patient prognosis.High-throughput virtual screening and subsequent experimental validation identified Dacarbazine as a pharmacological inhibitor of USP37,and its inhibition disrupted SND1 stability,hindering CRC cell proliferation and metastasis.This study reveals a novel and promising molecular mechanism driving CRC progression through the CDK1-SP37-ND1 axis,highlighting the clinical importance of targeting this pathway to improve patient outcomes.展开更多
The year 2024 marks the 60th anniversary of the discovery of the Epstein-Barr virus(EBV),the first virus confirmed to cause human cancer.Viral infections significantly contribute to the global cancer burden,with seven...The year 2024 marks the 60th anniversary of the discovery of the Epstein-Barr virus(EBV),the first virus confirmed to cause human cancer.Viral infections significantly contribute to the global cancer burden,with seven known Group 1 oncogenic viruses,including hepatitis B virus(HBV),human papillomavirus(HPV),EBV,Kaposi sarcoma-associated herpesvirus(KSHV),hepatitis C virus(HCV),human T-cell leukemia virus type 1(HTLV-1),and human immunodeficiency virus(HIV).These oncogenic viruses induce cellular transformation and cancer development by altering various biological processes within host cells,particularly under immunosuppression or co-carcinogenic exposures.These viruses are primarily associated with hepatocellular carcinoma,gastric cancer,cervical cancer,nasopharyngeal carcinoma,Kaposi sarcoma,lymphoma,and adult T-cell leukemia/lymphoma.Understanding the mechanisms of viral oncogenesis is crucial for identifying and characterizing the early biological processes of virus-related cancers,providing new targets and strategies for treatment or prevention.This review first outlines the global epidemiology of virus-related tumors,milestone events in research,and the process by which oncogenic viruses infect target cells.It then focuses on the molecular mechanisms by which these viruses induce tumors directly or indirectly,including the regulation of oncogenes or tumor suppressor genes,induction of genomic instability,disruption of regular life cycle of cells,immune suppression,chronic inflammation,and inducing angiogenesis.Finally,current therapeutic strategies for virus-related tumors and recent advances in preclinical and clinical research are discussed.展开更多
Lipocalin-2(LCN2)is a member of the lipocalin superfamily with multiple functions and can participate in the transport of a variety of small lipophilic ligands in vivo.LCN2 is significantly expressed in various tumors...Lipocalin-2(LCN2)is a member of the lipocalin superfamily with multiple functions and can participate in the transport of a variety of small lipophilic ligands in vivo.LCN2 is significantly expressed in various tumors and plays an important role in regulating tumor cell proliferation,invasion,and metastasis.The specific actions of LCN2 in tumors may vary depending on the particular type of cancer involved.In this review,we provide an extensive overview of the transcriptional and post-transcriptional regulation of LCN2 in health and disease.Furthermore,we summarize the impact of LCN2 dysregulation in a broad range of tumors.Lastly,we examine the mechanisms of action of LCN2 during tumorigenesis,progression,and metastasis.Understanding the complex relationships between LCN2 and tumor development,progression,and metastasis is vital for advancing our knowledge of cancer biology,developing biomarkers for diagnosis and clinical decision-making,and creating therapeutic strategies to improve the management of patients with cancer.展开更多
The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell d...The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell differentiation and function,and chronic unfolded protein response activation has been identified in bone disease.The unfolded protein response has been found to promote oncogenesis and drug resistance,raising the possibility that unfolded protein response modulators may have activity as anti-cancer agents.Cancer-associated bone disease remains a major cause of morbidity for patients with multiple myeloma or bone-metastatic disease.Understanding the critical role of unfolded protein response signaling in cancer development and metastasis,as well as its role in bone homeostasis,may lead to novel mechanisms by which to target cancer-associated bone disease.In this review,we summarize the current research delineating the roles of the unfolded protein response in bone biology and pathophysiology,and furthermore,review unfolded protein response modulating agents in the contexts of cancer and cancer-associated bone disease.展开更多
Gastric cancer is the second most common cancer worldwide and the second most common cause of cancer-related deaths. Despite complete resection of gastric cancer and lymph node dissection, as well as improvements in c...Gastric cancer is the second most common cancer worldwide and the second most common cause of cancer-related deaths. Despite complete resection of gastric cancer and lymph node dissection, as well as improvements in chemotherapy and radiotherapy, there are still 700 000 gastric cancer-related deaths per year worldwide and more than 80% of patients with advanced gastric cancer die of the disease or recurrent disease within 1 year after diagnosis. None of the treatment modalities we have been applying today can influence the overall survival rates:at present, the overall 5-year relative survival rate for gastric cancer is about 28%. Cellular metaplasia due to chronic inflammation, injury and repair are the most documented processes for neoplasia. It appears that chronic inflammation stimulates tumor development and plays a critical role in initiating, sustaining and advancing tumor growth. It is also evident that not all inflammation is tumorigenic. Additional mutations can be acquired, and this leads to the cancer cell gaining a further growth advantage and acquiring a more malignant phenotype. Intestinalization of gastric units, which is called "intestinal metaplasia"; phenotypic antralization of fundic units, which is called "spasmolytic polypeptide-expressing metaplasia"; and the development directly from the stem/progenitor cellzone are three pathways that have been described for gastric carcinogenesis. Also, an important factor for the development of gastrointestinal cancers is peritumoral stroma. However, the initiating cellular event in gastric metaplasia is still controversial. Understanding gastric carcinogenesis and its precursor lesions has been under intense investigation, and our paper attempts to highlight recent progress in this field of cancer research.展开更多
Helicobacter pylori infection(Hp-I)represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related fac...Helicobacter pylori infection(Hp-I)represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related factors,leading to inflammatory changes,dysbiosis and eventually gastric cancer.The normal gastric microbiota shows diversity,with Proteobacteria[Helicobacter pylori(H.pylori)belongs to this family],Firmicutes,Actinobacteria,Bacteroides and Fusobacteria being the most abundant phyla.Most studies indicate that H.pylori has inhibitory effects on the colonization of other bacteria,harboring a lower diversity of them in the stomach.When comparing the healthy with the diseased stomach,there is a change in the composition of the gastric microbiome with increasing abundance of H.pylori(where present)in the gastritis stage,while as the gastric carcinogenesis cascade progresses to gastric cancer,the oral and intestinal-type pathogenic microbial strains predominate.Hp-I creates a premalignant environment of atrophy and intestinal metaplasia and the subsequent alteration in gastric microbiota seems to play a crucial role in gastric tumorigenesis itself.Successful H.pylori eradication is suggested to restore gastric microbiota,at least in primary stages.It is more than clear that Hp-I,gastric microbiota and gastric cancer constitute a challenging tangle and the strong interaction between them makes it difficult to unroll.Future studies are considered of crucial importance to test the complex interaction on the modulation of the gastric microbiota by H.pylori as well as on the relationships between the gastric microbiota and gastric carcinogenesis.展开更多
Human papillomavirus(HPV) is one of the most common sexually transmitted infections worldwide. Exposure to HPV is very common,and an estimated 65%-100% of sexually active adults are exposed to HPV in their lifetime. T...Human papillomavirus(HPV) is one of the most common sexually transmitted infections worldwide. Exposure to HPV is very common,and an estimated 65%-100% of sexually active adults are exposed to HPV in their lifetime. The majority of HPV infections are asymptomatic,but there is a 10% chance that individuals will develop a persistent infection and have an increased risk of developing a carcinoma. The International Agency for Research on Cancer has found that the following cancer sites have a strong causal relationship with HPV: cervix uteri,penis,vulva,vagina,anus and oropharynx,including the base of the tongue and the tonsils. However,studies of the aetiological role of HPV in colorectal and esophageal malignancies have conflicting results. The aim of this review was to organize recent evidence and issues about the association between HPV infection and gastrointestinal tumours with a focus on esophageal,colorectal and anal cancers. The ultimate goal was to highlight possible implications for prognosis and prevention.展开更多
A recent work of Iliopoulos et al published in Cell highlighted a circuit orchestrated by microRNAs (miRNAs) that results in liver tumorigenesis and inflammation. This feedback loop, governed by miR-24 and miR-629, pr...A recent work of Iliopoulos et al published in Cell highlighted a circuit orchestrated by microRNAs (miRNAs) that results in liver tumorigenesis and inflammation. This feedback loop, governed by miR-24 and miR-629, promotes a hepatocyte nuclear factor-4α transient inhibition resulting in miR-124 induction and signal transducer and activator of transcription 3 activation. These promising data support the use of miRNA mimics or inhibitors as potent therapeutic approaches in liver cancer.展开更多
Formation of malignant tumor originating from normal healthy cell is a multistep process including genetic and epigenetic lesions. Previous studies of cell line model systems displayed that early important epigenetic ...Formation of malignant tumor originating from normal healthy cell is a multistep process including genetic and epigenetic lesions. Previous studies of cell line model systems displayed that early important epigenetic events happened in stepwise fashion prior to cell immortalization. Once these epigenetic alterations are integrated into chromatin, they will perform vertical propagation through cell subculture. Hence, status of epigenetics is dramatically important in maintaining of cell identity. Histone modification is another factor of epigenetic alterations during human oncogenesis. Histones, one of main components of chromatin, can be modified post-translationally. Histone tail modifications are regulated by corresponding modification enzymes. This review focuses on the description of relationship between the main sites of histone modification and oncogenesis.展开更多
AIM To clarify the prevalence of occult hepatitis B virus(HBV) infection(OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma(HCC), ...AIM To clarify the prevalence of occult hepatitis B virus(HBV) infection(OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma(HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus(HCV) infection. METHODS This prospective cohort study enrolled 174 patients with chronic HCV infection(chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or moredifferent viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. RESULTS The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively(P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response(SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. CONCLUSION The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.展开更多
Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention a...Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention and targeting of cancer therapy. Although nearly 20% of all cancers are caused by an infection of a microbe, the amount of evidence and information regarding the mechanisms associated with oncogenesis varies dramatically from one organism to the next. This review cannot be exhaustive because we are not aware of all infections worldwide in addition to their potential mechanisms for oncogenesis. More research is required for all of the species mentioned in this review.展开更多
Both viral diseases and cancer account for a large proportion of serious health problems. Viral infection and cancer are biologically and medically correlated and in many ways share common cellular pathways that lead ...Both viral diseases and cancer account for a large proportion of serious health problems. Viral infection and cancer are biologically and medically correlated and in many ways share common cellular pathways that lead to disease development or progression. Better understanding how these signaling events are specifically activated by different pathogenic stimuli and how they activate different downstream transcriptions in response to these stimuli at high specificity and efficiency will provide a new molecular basis for the development of novel disease biomarkers and therapeutic or preventive targets against both classes of diseases. Research in our laboratory has been prompted to investigate the regulation and modes of action of these pathways, with a more intensive focus on the NF-κB signaling, in the settings of severe or oncogenic viral infection as well as cancer development. It is hoped that our research will lead to eventual clinical application of biomarkers derived from these signaling pathways.展开更多
Objective:MicroRNA-188-5p(miR-188)enhances oncologic progression in various human malignancies.This study aimed to explore its role in colorectal cancer(CRC).Materials and Methods:Human CRC tissues paired with normal ...Objective:MicroRNA-188-5p(miR-188)enhances oncologic progression in various human malignancies.This study aimed to explore its role in colorectal cancer(CRC).Materials and Methods:Human CRC tissues paired with normal tissues,and several CRC cell lines were utilized.Real-time quantitative PCR was applied to measure the expression of miR-188.Overexpression and knockdown were used to access the function of miR-188 and to investigate whether FOXL1/Wnt signaling mediates such function.The proliferation,migration and invasion of cancer cells were evaluated by CCK8,wound-healing and transwell assays,respectively.Whether FOXL1 acted as a direct target of miR-188 was verified by dual-luciferase reporter assays.Results:Levels of miR-188 were upregulated in CRC tissues than in paired-normal tissues,as well as in various CRC cell lines.High expression of miR-188 was strongly associated with advanced tumor stage,accompanied with significant tumor cell proliferation,invasion and migration.It was confirmed that FOXL1 played positive crosstalk between miR-188 regulation and downstream Wnt/β-catenin signaling activation.Conclusions:All findings indicate that miR-188 promotes CRC cell proliferation and invasion through targeting FOXL1/Wnt signaling and could be served as a potential therapeutic target for human CRC in the future.展开更多
The growing interest in post-translational protein modification,particularly in SU-MOylation,is driven by its crucial role in cell cycle regulation.SUMOylation affects various cell cycle regulators,including oncogenes...The growing interest in post-translational protein modification,particularly in SU-MOylation,is driven by its crucial role in cell cycle regulation.SUMOylation affects various cell cycle regulators,including oncogenes,suggesting its relevance in cancer.SUMO E3 ligases are pivotal in this process,exhibiting diverse functionalities through structural domains and sub-cellular localizations.A less-explored SUMO E3 ligase,RANBP2,a component of the vertebrate nuclear pore complex,emerges as a central player in cellular cycle processes,as well as in tumorigenesis.The current studies illuminate the importance of RANBP2 and underscore the need for more extensive studies to validate its clinical applicability in neoplastic interventions.Our review elucidates the significance of RANBP2 across various types of malignancies.Addi-tionally,it delves into exploring RANBP2 as a prospective therapeutic target for cancer treat-ment,offering insights into the avenues that scholars should pursue in their subsequent research endeavors.Thus,further investigation into RANBP2’s role in solid tumorigenesis is eagerly awaited.展开更多
Dysregulation of histone deacetylases(HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has...Dysregulation of histone deacetylases(HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors(HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.展开更多
Over the past two decades, numerous non-coding RNAs(ncRNAs) have been identified in different biological systems including virology, especially in large DNA viruses such as herpesviruses. As a representative oncogenic...Over the past two decades, numerous non-coding RNAs(ncRNAs) have been identified in different biological systems including virology, especially in large DNA viruses such as herpesviruses. As a representative oncogenic alphaherpesvirus, Marek’s disease virus(MDV) causes an important immunosuppressive and rapid-onset neoplastic disease of poultry, namely Marek’s disease(MD). Vaccinations can efficiently prevent the onset of MD lymphomas and other clinical disease, often heralded as the first successful example of vaccination-based control of cancer. MDV infection is also an excellent model for research into virally-induced tumorigenesis. Recently, great progress has been made in understanding the functions of ncRNAs in MD biology.Herein, we give a review of the discovery and identification of MDV-encoded viral miRNAs, focusing on the genomics,expression profiles, and emerging critical roles of MDV-1 miRNAs as oncogenic miRNAs(oncomiRs) or tumor suppressor genes involved in the induction of MD lymphomas. We also described the involvements of host cellular miRNAs, lincRNAs, and circRNAs participating in MDV life cycle, pathogenesis, and/or tumorigenesis. The prospects, strategies, and new techniques such as the CRISPR/Cas9-based gene editing applicable for further investigation into the ncRNA-mediated regulatory mechanisms in MDV pathogenesis/oncogenesis were also discussed, together with the possibilities of future studies on antiviral therapy and the development of new efficient MD vaccines.展开更多
基金supported by the Sichuan Outstanding Youth Fund Project(23NSFJQ0099)the Chengdu Science and Technology Bureau(2024-YF05-02599-SN).
文摘The Ras/MAPK signaling cascade plays an essential role in the regulation of cellular processes,including proliferation,differentiation,and survival,serving as a pivotal intracellular communication network.Dysregulation of this pathway,frequently attributable to mutations within Ras genes,has been strongly associated with the development of a spectrum of cancers.This review underscores the pivotal role of the Ras/MAPK pathway in oncogenic transformation and tumor progression,briefing the intricate mechanisms through which the aberrant activation of this pathway leads to unbridled cell proliferation,inhibition of apoptosis,promotion of metastasis,and induction of angiogenesis,thereby providing valuable insights into the pathogenesis of malignancies.It also underscores the significance of the Ras/MAPK pathway as a therapeutic target and discusses the challenges and potential of targeted therapies,including combination treatments and personalized medicine approaches,to overcome resistance and enhance treatment efficacy in cancers driven by pathway dysregulation.
基金Supported by Grant-in-Aid for Scientific Research From the Ministry of Education,Culture,Science and Technology of Japan,No.21K07054(Hironori Yoshiyama)and No.22K07101(Hisashi Iizasa).
文摘Epstein-Barr virus(EBV)-associated gastric cancer(EBVaGC)cells originate from a single-cell clone infected with EBV.However,more than 95%of patients with gastric cancer have a history of Helicobacter pylori(H.pylori)infection,and H.pylori is a major causative agent of gastric cancer.Therefore,it has long been argued that H.pylori infection may affect the development of EBVaGC,a subtype of gastric cancer.Atrophic gastrointestinal inflammation,a symptom of H.pylori infection,is observed in the gastric mucosa of EBVaGC.Therefore,it remains unclear whether H.pylori infection is a cofactor for gastric carcinogenesis caused by EBV infection or whether H.pylori and EBV infections act independently on gastric cancer formation.It has been reported that EBV infection assists in the oncogenesis of gastric cancer caused by H.pylori infection.In contrast,several studies have reported that H.pylori infection accelerates tumorigenesis initiated by EBV infection.By reviewing both clinical epidemiological and experimental data,we reorganized the role of H.pylori and EBV infections in gastric cancer formation.
文摘The role that free radicals in general and oxygen radicals in particular play in carcinogenesis has attracted considerable attention in recent years. The oxygen radicals are undesirable but inevitable products of aerobic metabolism in the normal living cell. The cellular antioxidant defense system maintains an appropriate balance between necessary oxidative events and those that are excessive. When this critical balance cannot be maintained because of the overloading of the cellularredox system, oxygen radicals can induce cell damage. They can influence carcinogenesis by inducing DN A damage from direct oxidation or indirectly from DNA-binding products of lipid peroxidation. Oxygen radicals can induce conformational changes in the plasma membrane by lipid peroxidation and protein degradation, thus influencing membrane-associated cellular activities. They are capable of affecting membrane-bound protein kinases, growth factors and their receptors, and, therefore, signal transduction and oncogene activation. Thus, the oxygen radicals can have a major influence on oncogenes and oncogenesis. (C)1990 Academic Press.Inc.
基金Supported by the Associazione Italiana Ricerca sul Cancro,No.12182Cassini Project
文摘Pancreatic cancer is a lethal malignancy,whose precursor lesions are pancreatic intraepithelial neoplasm,intraductal papillary mucinous neoplasm,intraductal tubulopapillary neoplasm,and mucinous cystic neoplasm.To better understand the biology of pancreatic cancer,it is fundamental to know its precursors and to study the mechanisms of carcinogenesis.Each of these precursors displays peculiar histological features,as well as specific molecular alterations.Starting from such pre-invasive lesions,this review aims at summarizing the most important aspects of carcinogenesis of pancreatic cancer,with a specific focus on the recent advances and the future perspectives of the research on this lethal tumor type.
基金supported by the National Natural Science Foundation of China(Nos.82103543,82303235,U19A2008 and 82373232)Fundamental Research Funds for the Central Universities(No.WK9110000159,China)+1 种基金the Natural Science Foundation of Anhui Province(No.2108085QH340,China)the China Postdoctoral Science Foundation(No.2021M693082).
文摘Colorectal cancer(CRC)poses a severe global health challenge with high incidence and mortality rates.USP37 has been identified as the bona fide deubiquitinase of SND1,playing a critical role in stabilizing SND1,thereby augmenting its oncogenic potential.The interaction between USP37 and SND1 was confirmed through extensive proteomics,ubiquitinomics,and interactomics,underscoring their synergistic effects on CRC proliferation and metastasis.Additionally,CDK1 has emerged as a pivotal regulator of USP37,phosphorylating it at threonine 631 rather than serine 628,enhancing its deubiquitinase activity,and consequently stabilizing SND1 to drive CRC malignancy further.Histological analyses of human CRC samples linked the upregulation of CDK1 and USP37 with increased SND1 levels and poor patient prognosis.High-throughput virtual screening and subsequent experimental validation identified Dacarbazine as a pharmacological inhibitor of USP37,and its inhibition disrupted SND1 stability,hindering CRC cell proliferation and metastasis.This study reveals a novel and promising molecular mechanism driving CRC progression through the CDK1-SP37-ND1 axis,highlighting the clinical importance of targeting this pathway to improve patient outcomes.
基金supported by Chongqing Science and Health Joint Medical Research Sprint,Key Projects,and Major Projects(2025DBXM002)Chongqing Innovative Medical Device Application Demonstration Project(CQEIC2024MDAD-050)+5 种基金the Key Project of Chongqing Technology Innovation and Application Development Special Project(CSTB2024TIAD-KPX0031)National Natural ScienceFoundation of China(82370114)Special Project for Performance Incentive Guidance of Scientific Research Institutions(2024JXJL-YFX0022)Natural ScienceFoundation of Chongqing,China(CSTB2022NSCQ-MSX1150)the Fundamental Research Funds for the Central Universities(2022CDJYGRH-001)the Chongqing Professional Talents Plan(cstc2022ycjh-bgzxm0048).
文摘The year 2024 marks the 60th anniversary of the discovery of the Epstein-Barr virus(EBV),the first virus confirmed to cause human cancer.Viral infections significantly contribute to the global cancer burden,with seven known Group 1 oncogenic viruses,including hepatitis B virus(HBV),human papillomavirus(HPV),EBV,Kaposi sarcoma-associated herpesvirus(KSHV),hepatitis C virus(HCV),human T-cell leukemia virus type 1(HTLV-1),and human immunodeficiency virus(HIV).These oncogenic viruses induce cellular transformation and cancer development by altering various biological processes within host cells,particularly under immunosuppression or co-carcinogenic exposures.These viruses are primarily associated with hepatocellular carcinoma,gastric cancer,cervical cancer,nasopharyngeal carcinoma,Kaposi sarcoma,lymphoma,and adult T-cell leukemia/lymphoma.Understanding the mechanisms of viral oncogenesis is crucial for identifying and characterizing the early biological processes of virus-related cancers,providing new targets and strategies for treatment or prevention.This review first outlines the global epidemiology of virus-related tumors,milestone events in research,and the process by which oncogenic viruses infect target cells.It then focuses on the molecular mechanisms by which these viruses induce tumors directly or indirectly,including the regulation of oncogenes or tumor suppressor genes,induction of genomic instability,disruption of regular life cycle of cells,immune suppression,chronic inflammation,and inducing angiogenesis.Finally,current therapeutic strategies for virus-related tumors and recent advances in preclinical and clinical research are discussed.
基金supported by the Program for Science Technology and Innovation Committee of Shenzhen(2021N062-JCYJ20210324115408023)Guangdong High-Level Hospital Construction Fund,Shenzhen High-Level Hospital Construction Fund。
文摘Lipocalin-2(LCN2)is a member of the lipocalin superfamily with multiple functions and can participate in the transport of a variety of small lipophilic ligands in vivo.LCN2 is significantly expressed in various tumors and plays an important role in regulating tumor cell proliferation,invasion,and metastasis.The specific actions of LCN2 in tumors may vary depending on the particular type of cancer involved.In this review,we provide an extensive overview of the transcriptional and post-transcriptional regulation of LCN2 in health and disease.Furthermore,we summarize the impact of LCN2 dysregulation in a broad range of tumors.Lastly,we examine the mechanisms of action of LCN2 during tumorigenesis,progression,and metastasis.Understanding the complex relationships between LCN2 and tumor development,progression,and metastasis is vital for advancing our knowledge of cancer biology,developing biomarkers for diagnosis and clinical decision-making,and creating therapeutic strategies to improve the management of patients with cancer.
基金supported by the National Institutes of Health(Grants P30 CA036727 and R01 CA258621)and funding from the University of Nebraska Medical Center Graduate Studies Assistantship.
文摘The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell differentiation and function,and chronic unfolded protein response activation has been identified in bone disease.The unfolded protein response has been found to promote oncogenesis and drug resistance,raising the possibility that unfolded protein response modulators may have activity as anti-cancer agents.Cancer-associated bone disease remains a major cause of morbidity for patients with multiple myeloma or bone-metastatic disease.Understanding the critical role of unfolded protein response signaling in cancer development and metastasis,as well as its role in bone homeostasis,may lead to novel mechanisms by which to target cancer-associated bone disease.In this review,we summarize the current research delineating the roles of the unfolded protein response in bone biology and pathophysiology,and furthermore,review unfolded protein response modulating agents in the contexts of cancer and cancer-associated bone disease.
文摘Gastric cancer is the second most common cancer worldwide and the second most common cause of cancer-related deaths. Despite complete resection of gastric cancer and lymph node dissection, as well as improvements in chemotherapy and radiotherapy, there are still 700 000 gastric cancer-related deaths per year worldwide and more than 80% of patients with advanced gastric cancer die of the disease or recurrent disease within 1 year after diagnosis. None of the treatment modalities we have been applying today can influence the overall survival rates:at present, the overall 5-year relative survival rate for gastric cancer is about 28%. Cellular metaplasia due to chronic inflammation, injury and repair are the most documented processes for neoplasia. It appears that chronic inflammation stimulates tumor development and plays a critical role in initiating, sustaining and advancing tumor growth. It is also evident that not all inflammation is tumorigenic. Additional mutations can be acquired, and this leads to the cancer cell gaining a further growth advantage and acquiring a more malignant phenotype. Intestinalization of gastric units, which is called "intestinal metaplasia"; phenotypic antralization of fundic units, which is called "spasmolytic polypeptide-expressing metaplasia"; and the development directly from the stem/progenitor cellzone are three pathways that have been described for gastric carcinogenesis. Also, an important factor for the development of gastrointestinal cancers is peritumoral stroma. However, the initiating cellular event in gastric metaplasia is still controversial. Understanding gastric carcinogenesis and its precursor lesions has been under intense investigation, and our paper attempts to highlight recent progress in this field of cancer research.
文摘Helicobacter pylori infection(Hp-I)represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related factors,leading to inflammatory changes,dysbiosis and eventually gastric cancer.The normal gastric microbiota shows diversity,with Proteobacteria[Helicobacter pylori(H.pylori)belongs to this family],Firmicutes,Actinobacteria,Bacteroides and Fusobacteria being the most abundant phyla.Most studies indicate that H.pylori has inhibitory effects on the colonization of other bacteria,harboring a lower diversity of them in the stomach.When comparing the healthy with the diseased stomach,there is a change in the composition of the gastric microbiome with increasing abundance of H.pylori(where present)in the gastritis stage,while as the gastric carcinogenesis cascade progresses to gastric cancer,the oral and intestinal-type pathogenic microbial strains predominate.Hp-I creates a premalignant environment of atrophy and intestinal metaplasia and the subsequent alteration in gastric microbiota seems to play a crucial role in gastric tumorigenesis itself.Successful H.pylori eradication is suggested to restore gastric microbiota,at least in primary stages.It is more than clear that Hp-I,gastric microbiota and gastric cancer constitute a challenging tangle and the strong interaction between them makes it difficult to unroll.Future studies are considered of crucial importance to test the complex interaction on the modulation of the gastric microbiota by H.pylori as well as on the relationships between the gastric microbiota and gastric carcinogenesis.
文摘Human papillomavirus(HPV) is one of the most common sexually transmitted infections worldwide. Exposure to HPV is very common,and an estimated 65%-100% of sexually active adults are exposed to HPV in their lifetime. The majority of HPV infections are asymptomatic,but there is a 10% chance that individuals will develop a persistent infection and have an increased risk of developing a carcinoma. The International Agency for Research on Cancer has found that the following cancer sites have a strong causal relationship with HPV: cervix uteri,penis,vulva,vagina,anus and oropharynx,including the base of the tongue and the tonsils. However,studies of the aetiological role of HPV in colorectal and esophageal malignancies have conflicting results. The aim of this review was to organize recent evidence and issues about the association between HPV infection and gastrointestinal tumours with a focus on esophageal,colorectal and anal cancers. The ultimate goal was to highlight possible implications for prognosis and prevention.
文摘A recent work of Iliopoulos et al published in Cell highlighted a circuit orchestrated by microRNAs (miRNAs) that results in liver tumorigenesis and inflammation. This feedback loop, governed by miR-24 and miR-629, promotes a hepatocyte nuclear factor-4α transient inhibition resulting in miR-124 induction and signal transducer and activator of transcription 3 activation. These promising data support the use of miRNA mimics or inhibitors as potent therapeutic approaches in liver cancer.
基金Supported by the Natural Science Foundation of China(81173257)
文摘Formation of malignant tumor originating from normal healthy cell is a multistep process including genetic and epigenetic lesions. Previous studies of cell line model systems displayed that early important epigenetic events happened in stepwise fashion prior to cell immortalization. Once these epigenetic alterations are integrated into chromatin, they will perform vertical propagation through cell subculture. Hence, status of epigenetics is dramatically important in maintaining of cell identity. Histone modification is another factor of epigenetic alterations during human oncogenesis. Histones, one of main components of chromatin, can be modified post-translationally. Histone tail modifications are regulated by corresponding modification enzymes. This review focuses on the description of relationship between the main sites of histone modification and oncogenesis.
基金Supported by the Korea Centers for Disease Control and Prevention,No.4800-4859-304the Seoul National University Bundang Hospital,No.02-2014-026
文摘AIM To clarify the prevalence of occult hepatitis B virus(HBV) infection(OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma(HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus(HCV) infection. METHODS This prospective cohort study enrolled 174 patients with chronic HCV infection(chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or moredifferent viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. RESULTS The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively(P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response(SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. CONCLUSION The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.
文摘Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention and targeting of cancer therapy. Although nearly 20% of all cancers are caused by an infection of a microbe, the amount of evidence and information regarding the mechanisms associated with oncogenesis varies dramatically from one organism to the next. This review cannot be exhaustive because we are not aware of all infections worldwide in addition to their potential mechanisms for oncogenesis. More research is required for all of the species mentioned in this review.
基金National Natural Science Foundation of China (30872930)Guangdong Provincial Natural Science Foundation (2006Z3-E4081and 2007A03260001)Science and Technology Department of Zhuhai Municipality (PC20071076)
文摘Both viral diseases and cancer account for a large proportion of serious health problems. Viral infection and cancer are biologically and medically correlated and in many ways share common cellular pathways that lead to disease development or progression. Better understanding how these signaling events are specifically activated by different pathogenic stimuli and how they activate different downstream transcriptions in response to these stimuli at high specificity and efficiency will provide a new molecular basis for the development of novel disease biomarkers and therapeutic or preventive targets against both classes of diseases. Research in our laboratory has been prompted to investigate the regulation and modes of action of these pathways, with a more intensive focus on the NF-κB signaling, in the settings of severe or oncogenic viral infection as well as cancer development. It is hoped that our research will lead to eventual clinical application of biomarkers derived from these signaling pathways.
基金supported by the Science and Technology Development Project of Guangzhou(201904010036)the Natural Science Foundation of Guangdong(2018A030313715)+1 种基金National Natural Science Foundation of China(81871908)National Key R&D Program of China(Nos.2017YFC1308800,2017YFC1308803).
文摘Objective:MicroRNA-188-5p(miR-188)enhances oncologic progression in various human malignancies.This study aimed to explore its role in colorectal cancer(CRC).Materials and Methods:Human CRC tissues paired with normal tissues,and several CRC cell lines were utilized.Real-time quantitative PCR was applied to measure the expression of miR-188.Overexpression and knockdown were used to access the function of miR-188 and to investigate whether FOXL1/Wnt signaling mediates such function.The proliferation,migration and invasion of cancer cells were evaluated by CCK8,wound-healing and transwell assays,respectively.Whether FOXL1 acted as a direct target of miR-188 was verified by dual-luciferase reporter assays.Results:Levels of miR-188 were upregulated in CRC tissues than in paired-normal tissues,as well as in various CRC cell lines.High expression of miR-188 was strongly associated with advanced tumor stage,accompanied with significant tumor cell proliferation,invasion and migration.It was confirmed that FOXL1 played positive crosstalk between miR-188 regulation and downstream Wnt/β-catenin signaling activation.Conclusions:All findings indicate that miR-188 promotes CRC cell proliferation and invasion through targeting FOXL1/Wnt signaling and could be served as a potential therapeutic target for human CRC in the future.
基金supported by the National Natural Science Foundation of China(No.82273457)the Guangdong Basic and Applied Basic Research Foundation of China(No.2023A1515012762 and 2021A1515010846)+2 种基金Special Grant for Key Area Programs of Guangdong Education Department(China)(No.2021ZDZX2040)Science and Technology Special Project of Guangdong Province,China(No.210715216902829)“Dengfeng Project”for the construction of high-level hospitals in Guangdong Provinced First Affiliated Hospital of Shantou University College Supporting Funding(No.202003-10).
文摘The growing interest in post-translational protein modification,particularly in SU-MOylation,is driven by its crucial role in cell cycle regulation.SUMOylation affects various cell cycle regulators,including oncogenes,suggesting its relevance in cancer.SUMO E3 ligases are pivotal in this process,exhibiting diverse functionalities through structural domains and sub-cellular localizations.A less-explored SUMO E3 ligase,RANBP2,a component of the vertebrate nuclear pore complex,emerges as a central player in cellular cycle processes,as well as in tumorigenesis.The current studies illuminate the importance of RANBP2 and underscore the need for more extensive studies to validate its clinical applicability in neoplastic interventions.Our review elucidates the significance of RANBP2 across various types of malignancies.Addi-tionally,it delves into exploring RANBP2 as a prospective therapeutic target for cancer treat-ment,offering insights into the avenues that scholars should pursue in their subsequent research endeavors.Thus,further investigation into RANBP2’s role in solid tumorigenesis is eagerly awaited.
基金supported by the National Natural Science Foundation of China (81874288, 82003590 and 92053105)the Natural Science Foundation of Shandong Province (ZR2020QH342, China)+1 种基金the Key Project of Natural Science Foundation of Anhui Province for College Scholar (2022AH051216, China)Scientific Research Project of Anhui Provincial Health Commission (AHWJ2022b005, China)。
文摘Dysregulation of histone deacetylases(HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors(HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.
基金supported by the National Natural Science Foundation of China(U21A20260)the Natural Science Foundation of Henan Province(212300410359)+1 种基金the Independent innovation project of Henan Academy of Agricultural Sciences(2022ZC65)the BBSRC Newton Fund Joint Centre Awards on“UK-China Centre of Excellence for Research on Avian Diseases”(BBS/OS/NW/000007)。
文摘Over the past two decades, numerous non-coding RNAs(ncRNAs) have been identified in different biological systems including virology, especially in large DNA viruses such as herpesviruses. As a representative oncogenic alphaherpesvirus, Marek’s disease virus(MDV) causes an important immunosuppressive and rapid-onset neoplastic disease of poultry, namely Marek’s disease(MD). Vaccinations can efficiently prevent the onset of MD lymphomas and other clinical disease, often heralded as the first successful example of vaccination-based control of cancer. MDV infection is also an excellent model for research into virally-induced tumorigenesis. Recently, great progress has been made in understanding the functions of ncRNAs in MD biology.Herein, we give a review of the discovery and identification of MDV-encoded viral miRNAs, focusing on the genomics,expression profiles, and emerging critical roles of MDV-1 miRNAs as oncogenic miRNAs(oncomiRs) or tumor suppressor genes involved in the induction of MD lymphomas. We also described the involvements of host cellular miRNAs, lincRNAs, and circRNAs participating in MDV life cycle, pathogenesis, and/or tumorigenesis. The prospects, strategies, and new techniques such as the CRISPR/Cas9-based gene editing applicable for further investigation into the ncRNA-mediated regulatory mechanisms in MDV pathogenesis/oncogenesis were also discussed, together with the possibilities of future studies on antiviral therapy and the development of new efficient MD vaccines.
