This article reviews the relationship between copper and ischemic heart disease,the antioxidant and angiogenic effects of ischemia inducible factors,the mechanism of copper regulating HIF-1 transcription activity,the ...This article reviews the relationship between copper and ischemic heart disease,the antioxidant and angiogenic effects of ischemia inducible factors,the mechanism of copper regulating HIF-1 transcription activity,the mechanism of copper promoting angiogenesis and the research progress of TETA-Cu,hoping to provide a reference for future clinical research.展开更多
This paper reviewed the shortcomings of conventional therapies for ischemic stroke and discussed the methods of vascular regeneration,stem cell differentiation,homing and neuronal remodeling after ischemic stroke,to p...This paper reviewed the shortcomings of conventional therapies for ischemic stroke and discussed the methods of vascular regeneration,stem cell differentiation,homing and neuronal remodeling after ischemic stroke,to provide potential therapeutic ideas for ischemic stroke.展开更多
Nasopharyngeal carcinoma(NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia.Alternative to genetic changes,aberrant epigenetic events disrupt multiple genes in...Nasopharyngeal carcinoma(NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia.Alternative to genetic changes,aberrant epigenetic events disrupt multiple genes involved in cell signaling pathways through DNA methylation of promoter CpG islands and/or histone modifications.These epigenetic alterations grant cell growth advantage and contribute to the initiation and progression of NPC.In this review,we summarize the epigenetic deregulation of cell signaling in NPC tumorigenesis and highlight the importance of identifying epigenetic cell signaling regulators in NPC research.Developing pharmacologic strategies to reverse the epigenetic-silencing of cell signaling regulators might thus be useful to NPC prevention and therapy.展开更多
Latent membrane protein 1 (LMP1), an important protein encoded by Epstein Barr virus (EBV), has been implied to link with the pathogenesis of nasopharyngeal carcinoma (NPC). Its dual effects of increasing cell prolife...Latent membrane protein 1 (LMP1), an important protein encoded by Epstein Barr virus (EBV), has been implied to link with the pathogenesis of nasopharyngeal carcinoma (NPC). Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line- CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G2/M phase, our studies suggested that LMP1 could promote the expression of Survivin in G0/G1, S and G2/ M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMP1. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.展开更多
Viral infections contribute to approximately 12%of cancers worldwide,with the vast majority occurring in developing countries and areas.Two DNA viruses,Epstein-Barr virus(EBV) and human papillomavirus(HPV),are associa...Viral infections contribute to approximately 12%of cancers worldwide,with the vast majority occurring in developing countries and areas.Two DNA viruses,Epstein-Barr virus(EBV) and human papillomavirus(HPV),are associated with38%of all virus-associated cancers.The probability of one patient infected with these two distinct types of viruses is increasing.Here,we summarize the co-infection of EBV and HPV in human malignancies and address the possible mechanisms for the co-infection of EBV and HPV during tumorigenesis.展开更多
Objective:To measure the expression pattern of STAT2 in cenical cancer initiation and progression in tissue sections from patients with cervicitis,dysplasia,and cenical cancer. Methods:Antibody against human STAT2 was...Objective:To measure the expression pattern of STAT2 in cenical cancer initiation and progression in tissue sections from patients with cervicitis,dysplasia,and cenical cancer. Methods:Antibody against human STAT2 was confirmed by plasmids transient transfection and Western blot Immunohistochemistry was used to delect STAT2 expression in the cervical biopsies by using the confirmed antibody against STAT2 as the primary antibody.Results:It was found that the overall rate of positive STAT2 expression in the cervicitis,dysplasia and cenical cancer groups were 38.5%,69.49%and 76.991,respectively.The STAT2 levels are significantly increased in premalignant dysplasia and cervical cancer,as compared lo cervicitis(P【 0.05). Noticeably,STAT2 signals were mainly found in the cytoplasm,implying that STAT2 was not biologically active.Conclusions:These findings reveal an association between cenical cancer progression and augmented STAT2 expression.In conclusion.STAT2 increase appears to be an early detectable cellular event in cenical cancer development.展开更多
Spiders are among the most varied terrestrial predators,with highly diverse morphology,ecology,and behavior.Morphological and molecular data have greatly contributed to advances in the phylogeny and evolutionary dynam...Spiders are among the most varied terrestrial predators,with highly diverse morphology,ecology,and behavior.Morphological and molecular data have greatly contributed to advances in the phylogeny and evolutionary dynamics of spiders.Here,we performed comprehensive mitochondrial phylogenomics analysis on 78 mitochondrial genomes(mitogenomes)representing 29 families;of these,23 species from eight families were newly generated.Mesothelae retained the same gene arrangement as the arthropod ancestor(Limulus polyphemus),while Opisthothelae showed extensive rearrangement,with 12 rearrangement types in transfer RNAs(tRNAs)and control region.Most spider tRNAs were extremely truncated and lacked typical dihydrouridine or TΨC arms,showing high tRNA structural diversity;in particular,trnS1 exhibited anticodon diversity across the phylogeny.The evolutionary rates of mitochondrial genes were potentially associated with gene rearrangement or truncated tRNAs.Both mitogenomic sequences and rearrangements possessed phylogenetic characteristics,providing a robust backbone for spider phylogeny,as previously reported.The monophyly of suborder,infraorder,retrolateral tibial apophysis clade,and families(except for Pisauridae)was separately supported,and high-level relationships were resolved as(Mesothelae,(Mygalomorphae,(Entelegynae,(Synspermiata,Hypochilidae)))).The phylogenetic positions of several families were also resolved(e.g.,Eresidae,Oecobiidae and Titanoecidae).Two reconstructions of ancestral web type obtained almost identical results,indicating that the common ancestor of spiders likely foraged using a silk-lined burrow.This study,the largest mitochondrial phylogenomics analysis of spiders to date,highlights the usefulness of mitogenomic data not only for providing efficient phylogenetic signals for spider phylogeny,but also for characterizing trait diversification in spider evolution.展开更多
Correction to:Signal Transduction and Targeted Therapy(2020)5:56,https://doi.org/10.1038/s41392-020-0151-9,published online 20 May 2020 In this article1 an error was noticed in Fig.3d left(p-Drp1 Ser637).The images we...Correction to:Signal Transduction and Targeted Therapy(2020)5:56,https://doi.org/10.1038/s41392-020-0151-9,published online 20 May 2020 In this article1 an error was noticed in Fig.3d left(p-Drp1 Ser637).The images were misassigned.And one writing error was found in Fig.S1c.The correct figures are given.The authors confirm that these corrections do not change the result interpretation or conclusions of the article.展开更多
It is generally believed that the expression of a gene is restricted "within the right place and at the right time". This principle has long been considered applicable as well to the expression of immunoglobulin (I...It is generally believed that the expression of a gene is restricted "within the right place and at the right time". This principle has long been considered applicable as well to the expression of immunoglobulin (Ig) lymphocytes of B cell lineage. However, increasing evidence has shown Ig "paradoxically" expressed in malignant tumors of epithelial origin. We reviewed the recent progress in the study of cancer-derived Ig, and also discussed its mechanisms and possible functions, trying to arouse interest and attention to those working in the field of immunology and oncology.展开更多
To explore the significance of cancerous immunoglobulin(Ig)in cancer cell growth,HeLa cervical cancer cells were stably transfected with small interfering RNA(siRNA)that specifically,efficiently and consistently silen...To explore the significance of cancerous immunoglobulin(Ig)in cancer cell growth,HeLa cervical cancer cells were stably transfected with small interfering RNA(siRNA)that specifically,efficiently and consistently silences the expression of heavy chain genes of all immunoglobulin isotypes.This stable cell line was used to examine cell viability,colony formation and tumor growth in athymic nude mice.The results of these experiments indicated that siRNA-mediated knockdown of cancerous Ig inhibited cell growth in vitro and suppressed tumor cell growth in immune-deficient nude mice in vivo.Similarly,this siRNA also inhibited the growth of MGC gastric cancer cells and MCF-7 breast cancer cells.Furthermore,the presence of cancerous Ig specifically reduced antibody-dependent cell-mediated cytotoxicity(ADCC)induced by an anti-human epithelial growth factor receptor(EGFR)antibody in a dose-dependent manner,suggesting that the cancerous Ig-Fc receptor interaction inhibits natural killer cell(or NK cell)effector function.The prevalent expression of Ig in human carcinomas and its capacity to promote growth and inhibit immunity might have important implications in growth regulation and targeted therapy for human cancers.展开更多
Accumulating evidence has shown that immunoglobulin(Ig)is‘unexpectedly’expressed by epithelial cancer cells and that it can promote tumor growth.The main purpose of this study was to explore the components of the ca...Accumulating evidence has shown that immunoglobulin(Ig)is‘unexpectedly’expressed by epithelial cancer cells and that it can promote tumor growth.The main purpose of this study was to explore the components of the cancerous Ig and its possible function.The presence of cancerous Ig in the Golgi apparatus was confirmed by immunofluorescence,indirectly suggesting that the cancerous Ig was processed and packaged in cancer cells.Western blot analysis and ELISA results indicated that cancer cells produced membrane Ig and secreted Ig into the supernatant fraction.The cancerous Ig consists of an a heavy chain and a k light chain.Finally,by analyzing the Ig components pulled down by protein A beads,the cancerous Ig was found to be structurally distinct from normal Ig.The cancerous Ig was truncated or aberrant.Although the underlying mechanism that causes the abnormalities has not been determined,our current discoveries strengthen our previous findings and promise fruitful future explorations.展开更多
In this work,the lamellar structural evolution and microvoids variations of βpolypropylene(β-PP)during the processing of two different stretching methods,sequential biaxial stretching and simultaneous biaxial stretc...In this work,the lamellar structural evolution and microvoids variations of βpolypropylene(β-PP)during the processing of two different stretching methods,sequential biaxial stretching and simultaneous biaxial stretching,were investigated in detail.It was found that different stretching methods led to significantly different lamellae deformation modes,and the microporous membranes obtained from the simultaneous biaxial stretching exhibited better mechanical properties.For the sequential biaxial stretching,abundant coarse fibers originated from the tight accumulation of the lamellae parallel to the longitudinal stretching direction,whereas the lamellae perpendicular to the stretching direction were easily deformed and separated.Those coarse fibers were difficult to be separated to form micropores during the subsequent transverse stretching process,resulting in a poor micropores distribution.However,for the simultaneous biaxial stretching,theβcrystal had the same deformation mode,that is,the lamellae distributed in different directions were all destroyed,forming abundant microvoids and little coarse fibers.展开更多
Immunoglobulins (Igs) are known to be synthesized and secreted only by B lymphocytes. Class switch recombination (CSR) is a key event that enables B cells to express Igs, and one of the crucial steps for CSR initi...Immunoglobulins (Igs) are known to be synthesized and secreted only by B lymphocytes. Class switch recombination (CSR) is a key event that enables B cells to express Igs, and one of the crucial steps for CSR initiation is the germline transcription of Iggenes. Surprisingly, recent studies have demonstrated that the Iggenes are also expressed in some epithelial cancer cells; however, the mechanisms underlying how cancer cells initiate CSR and express Igs are still unknown. In this study, we confirmed that the Ig la I promoter in cancer cell lines was activated by the Ets- 1 transcription factor, and the activity of the Ig la I promoter and ig lal-C^l germiine transcription were attenuated after knockdown of Ets-1 by specific small interfering RNAs (siRNA). Furthermore, the expression of Ets-1 and Iga heavy chain in cancer cells was dose dependently upregulated by TGF-I^I. These results indicate that activation of the Ig lal promoter by the transcriotion factor Ets-1 is a critical Dathwav and orovides a novel mechanism for le exoression in non-B cell cancers.展开更多
This paper reports a novel method to detect human leukemic lymphoblasts(CCRF-CEM cells).While the aptamer of the cancer cells was employed as the recognition element to target cancer cells,peroxidaseactive DNAzyme was...This paper reports a novel method to detect human leukemic lymphoblasts(CCRF-CEM cells).While the aptamer of the cancer cells was employed as the recognition element to target cancer cells,peroxidaseactive DNAzyme was used as the sensing element to produce catalysis-induced colorimetric signals.The elegant architecture integrating the aptamer and DNAzyme made it feasible to detect cancer cells easily and rapidly by the color change of the substrate for DNAzyme.Experimental results showed that 500 cells can well indicate the cancer,while as control,250,000 Islet Island Beta cells only show tiny signals,suggesting that the method proposed in this paper has considerable sensitivity and selectivity.Furthermore,since it does not require expensive apparatus,or modification or label of DNA chains,the method we present here is also costeffective and conveniently operated,implying potential applications in future cancer diagnosis.展开更多
Latent membrane protein 1(LMP1)is a major Epstein–Barr virus(EBV)-encoded oncoprotein involved in latency infection that regulates mitochondrial functions to facilitate cell survival.Recently,mitochondrial fission ha...Latent membrane protein 1(LMP1)is a major Epstein–Barr virus(EBV)-encoded oncoprotein involved in latency infection that regulates mitochondrial functions to facilitate cell survival.Recently,mitochondrial fission has been demonstrated as a crucial mechanism in oncovirus-mediated carcinogenesis.Mitochondrial dynamin-related protein 1(Drp1)-mediated mitochondrial fission has an impact on the chemoresistance of cancers.However,the mechanism by which oncogenic stress promotes mitochondrial fission,potentially contributing to tumorigenesis,is not entirely understood.The role of Drp1 in the oncogenesis and prognosis of EBV-LMP1-positive nasopharyngeal carcinoma(NPC)was determined in our study.We show that EBV-LMP1 exhibits a new function in remodeling mitochondrial morphology by activating Drp1.A high level of p-Drp1(Ser616)or a low level of p-Drp1(Ser637)correlates with poor overall survival and disease-free survival.Furthermore,the protein level of p-Drp1(Ser616)is related to the clinical stage(TNM stage)of NPC.Targeting Drp1 impairs mitochondrial function and induces cell death in LMP1-positive NPC cells.In addition,EBV-LMP1 regulates Drp1 through two oncogenic signaling axes,AMPK and cyclin B1/Cdk1,which promote cell survival and cisplatin resistance in NPC.Our findings provide novel insight into the role of EBV-LMP1-driven mitochondrial fission in regulating Drp1 phosphorylation at serine 616 and serine 637.Disruption of Drp1 could be a promising therapeutic strategy for LMP1-positive NPC.展开更多
Cancer stem cells(CSCs)exhibit highly aggressive and metastatic features and resistance to chemotherapy and radiotherapy.Aryl hydrocarbon receptor(AhR)expression varies among non-small cell lung cancers(NSCLCs),and th...Cancer stem cells(CSCs)exhibit highly aggressive and metastatic features and resistance to chemotherapy and radiotherapy.Aryl hydrocarbon receptor(AhR)expression varies among non-small cell lung cancers(NSCLCs),and the mechanisms that support abnormal AhR expression in CSCs remain elusive.Here,we identified ubiquitin carboxyl terminal hydrolase L3(UCHL3),a DUB enzyme in the UCH protease family,as a bona fide deubiquitylase of the AhR in NSCLC.UCHL3 was shown to interact with,deubiquitylate,and stabilize AhR in a manner dependent on its deubiquitylation activity.Moreover,we showed that UCHL3 promotes the stem-like characteristics and potent tumorigenic capacity of NSCLC cells.UCHL3 increased AhR stability and the binding of AhR to the promoter regions of the“stemness”genes ATP-binding cassette subfamily G member 2(ABCG2),KLF4,and c-Myc.Depletion of UCHL3 markedly downregulated the“stemness”genes ABCG2,KLF4,and c-Myc,leading to the loss of selfrenewal and tumorigenesis in NSCLCs.Furthermore,the UCHL3 inhibitor TCID induced AhR degradation and exhibited significantly attenuated efficacy in NSCLC cells with stem cell-like properties.Additionally,UCHL3 was shown to indicate poor prognosis in patients with lung adenocarcinoma.In general,our results reveal that the UCHL3 deubiquitylase is pivotal for AhR protein stability and a potential target for NSCLC-targeted therapy.展开更多
Recently, immunoglobulins (Igs) were unexpectedly found to be expressed in epithelial cancers. Immunoglobulin class switching or class switch recombination (CSR) is a natural biological process that alters a B cel...Recently, immunoglobulins (Igs) were unexpectedly found to be expressed in epithelial cancers. Immunoglobulin class switching or class switch recombination (CSR) is a natural biological process that alters a B cell's production of antibodies (immunoglobulins) from one class to another. However, the mechanism of CSR of Iggenes in cancer is still unknown. Here, we confirmed by detecting the hallmark of CSR that the Iga gene in cancer underwent CSR. Then we focused on activation-induced cytidine deaminase (AID), a crucial factor for initiating CSR. Further studies using tumor necrosis factor (TNF)-α stimulation and specific inhibitor of NF-KB revealed that TNF-α could increase AID expression through NF-κB signaling. Finally, we demonstrated that AID could co-localize with protein kinase A and bind to the switching (Sα) region of the Igα gene. Overexpression of AID obviously enhanced Igα heavy chain expression and its binding ability to the Sa region. These findings indicated that TNF-α-induced AID expression is involved with CSR in cancer.展开更多
Epstein-Barr virus-associated diseases are important global health concerns.As a group I carcinogen,EBV accounts for 1.5%of human malignances,including both epithelial-and lymphatic-originated tumors.Moreover,EBV play...Epstein-Barr virus-associated diseases are important global health concerns.As a group I carcinogen,EBV accounts for 1.5%of human malignances,including both epithelial-and lymphatic-originated tumors.Moreover,EBV plays an etiological and pathogenic role in a number of non-neoplastic diseases,and is even involved in multiple autoimmune diseases(SADs).In this review,we summarize and discuss some recent exciting discoveries in EBV research area,which including DNA methylation alterations,metabolic reprogramming,the changes of mitochondria and ubiquitin-proteasome system(UPS),oxidative stress and EBV lytic reactivation,variations in non-coding RNA(ncRNA),radiochemotherapy and immunotherapy.Understanding and learning from this advancement will further confrm the far-reaching and future value of therapeutic strategies in EBV-associated diseases.展开更多
文摘This article reviews the relationship between copper and ischemic heart disease,the antioxidant and angiogenic effects of ischemia inducible factors,the mechanism of copper regulating HIF-1 transcription activity,the mechanism of copper promoting angiogenesis and the research progress of TETA-Cu,hoping to provide a reference for future clinical research.
文摘This paper reviewed the shortcomings of conventional therapies for ischemic stroke and discussed the methods of vascular regeneration,stem cell differentiation,homing and neuronal remodeling after ischemic stroke,to provide potential therapeutic ideas for ischemic stroke.
基金supported by grants from Hong Kong RGC (GRF #473908 and #475009)National Natural Science Foundation of China (No. 81071634)
文摘Nasopharyngeal carcinoma(NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia.Alternative to genetic changes,aberrant epigenetic events disrupt multiple genes involved in cell signaling pathways through DNA methylation of promoter CpG islands and/or histone modifications.These epigenetic alterations grant cell growth advantage and contribute to the initiation and progression of NPC.In this review,we summarize the epigenetic deregulation of cell signaling in NPC tumorigenesis and highlight the importance of identifying epigenetic cell signaling regulators in NPC research.Developing pharmacologic strategies to reverse the epigenetic-silencing of cell signaling regulators might thus be useful to NPC prevention and therapy.
基金National Nature Science Foundation for Distinguished Young Scholar of China (No.39525022)National Basic Research Program(No.2004CB518703) National Nature Science Foundation of China (No.30570085).
文摘Latent membrane protein 1 (LMP1), an important protein encoded by Epstein Barr virus (EBV), has been implied to link with the pathogenesis of nasopharyngeal carcinoma (NPC). Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line- CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G2/M phase, our studies suggested that LMP1 could promote the expression of Survivin in G0/G1, S and G2/ M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMP1. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.
基金supported by the National Basic Research Program of China[2011CB504300(Y.T.Y.C.),2015CB553903(Y.T.)]+2 种基金the National High Technology Research and Development Program of China(863 Program)[2012AA02A501(Y.C.)]the National Natural Science Foundation of China[81,171,881 and81372427(Y.T.),81271763(S.L.),81,302,354(Y.S.)]the Hunan Natural Science Foundation of China[12JJ1013(Y.T.)]
文摘Viral infections contribute to approximately 12%of cancers worldwide,with the vast majority occurring in developing countries and areas.Two DNA viruses,Epstein-Barr virus(EBV) and human papillomavirus(HPV),are associated with38%of all virus-associated cancers.The probability of one patient infected with these two distinct types of viruses is increasing.Here,we summarize the co-infection of EBV and HPV in human malignancies and address the possible mechanisms for the co-infection of EBV and HPV during tumorigenesis.
基金funded by 'Chinese National Nature Science Foundation(30771122)''Chinese Ministry of Education,Research Start-up Funding for Home Smdents' to Ming Li
文摘Objective:To measure the expression pattern of STAT2 in cenical cancer initiation and progression in tissue sections from patients with cervicitis,dysplasia,and cenical cancer. Methods:Antibody against human STAT2 was confirmed by plasmids transient transfection and Western blot Immunohistochemistry was used to delect STAT2 expression in the cervical biopsies by using the confirmed antibody against STAT2 as the primary antibody.Results:It was found that the overall rate of positive STAT2 expression in the cervicitis,dysplasia and cenical cancer groups were 38.5%,69.49%and 76.991,respectively.The STAT2 levels are significantly increased in premalignant dysplasia and cervical cancer,as compared lo cervicitis(P【 0.05). Noticeably,STAT2 signals were mainly found in the cytoplasm,implying that STAT2 was not biologically active.Conclusions:These findings reveal an association between cenical cancer progression and augmented STAT2 expression.In conclusion.STAT2 increase appears to be an early detectable cellular event in cenical cancer development.
基金supported by the Second Tibetan Plateau Scientific Expedition and Research(STEP)Program(2019QZKK0302)Natural Science Foundation of Gansu Province(20JR5RA252)Innovation and Entrepreneurship Project of Lanzhou University(20210010020,20210010002)。
文摘Spiders are among the most varied terrestrial predators,with highly diverse morphology,ecology,and behavior.Morphological and molecular data have greatly contributed to advances in the phylogeny and evolutionary dynamics of spiders.Here,we performed comprehensive mitochondrial phylogenomics analysis on 78 mitochondrial genomes(mitogenomes)representing 29 families;of these,23 species from eight families were newly generated.Mesothelae retained the same gene arrangement as the arthropod ancestor(Limulus polyphemus),while Opisthothelae showed extensive rearrangement,with 12 rearrangement types in transfer RNAs(tRNAs)and control region.Most spider tRNAs were extremely truncated and lacked typical dihydrouridine or TΨC arms,showing high tRNA structural diversity;in particular,trnS1 exhibited anticodon diversity across the phylogeny.The evolutionary rates of mitochondrial genes were potentially associated with gene rearrangement or truncated tRNAs.Both mitogenomic sequences and rearrangements possessed phylogenetic characteristics,providing a robust backbone for spider phylogeny,as previously reported.The monophyly of suborder,infraorder,retrolateral tibial apophysis clade,and families(except for Pisauridae)was separately supported,and high-level relationships were resolved as(Mesothelae,(Mygalomorphae,(Entelegynae,(Synspermiata,Hypochilidae)))).The phylogenetic positions of several families were also resolved(e.g.,Eresidae,Oecobiidae and Titanoecidae).Two reconstructions of ancestral web type obtained almost identical results,indicating that the common ancestor of spiders likely foraged using a silk-lined burrow.This study,the largest mitochondrial phylogenomics analysis of spiders to date,highlights the usefulness of mitogenomic data not only for providing efficient phylogenetic signals for spider phylogeny,but also for characterizing trait diversification in spider evolution.
文摘Correction to:Signal Transduction and Targeted Therapy(2020)5:56,https://doi.org/10.1038/s41392-020-0151-9,published online 20 May 2020 In this article1 an error was noticed in Fig.3d left(p-Drp1 Ser637).The images were misassigned.And one writing error was found in Fig.S1c.The correct figures are given.The authors confirm that these corrections do not change the result interpretation or conclusions of the article.
基金grants from China Medicine Board (No. 96655, No. 04-799)State Key Basic Research andDevelopment Plan (973) of the Ministry of Science and Technology of China (No. 2004CB518703)+4 种基金National High Technology Research and Development Program (863) of China (No. 2006AA02A404)Key Project of National Natural Science Foundation of China (No. 38930410, No. 30530710)National Natural Science Foundation of China (No. 39080015, No. 39400153, No. 39470299, No. 39600082, No. 69700170, No. 30171047, No. 30271218, No. 30471968, No. 30570700, No. 30772465)National Natural Science Funds for Distinguished Young Scholar (No. 39525022)Key Project of Hunan Province (04SK1001).
文摘It is generally believed that the expression of a gene is restricted "within the right place and at the right time". This principle has long been considered applicable as well to the expression of immunoglobulin (Ig) lymphocytes of B cell lineage. However, increasing evidence has shown Ig "paradoxically" expressed in malignant tumors of epithelial origin. We reviewed the recent progress in the study of cancer-derived Ig, and also discussed its mechanisms and possible functions, trying to arouse interest and attention to those working in the field of immunology and oncology.
基金the Major Program of National Natural Science Foundation of China(39830410)National High Technology Research and Development Program(863)of China(2006AA02A404)CMB project(99665)and National Natural Science Foundation of China(30772465).
文摘To explore the significance of cancerous immunoglobulin(Ig)in cancer cell growth,HeLa cervical cancer cells were stably transfected with small interfering RNA(siRNA)that specifically,efficiently and consistently silences the expression of heavy chain genes of all immunoglobulin isotypes.This stable cell line was used to examine cell viability,colony formation and tumor growth in athymic nude mice.The results of these experiments indicated that siRNA-mediated knockdown of cancerous Ig inhibited cell growth in vitro and suppressed tumor cell growth in immune-deficient nude mice in vivo.Similarly,this siRNA also inhibited the growth of MGC gastric cancer cells and MCF-7 breast cancer cells.Furthermore,the presence of cancerous Ig specifically reduced antibody-dependent cell-mediated cytotoxicity(ADCC)induced by an anti-human epithelial growth factor receptor(EGFR)antibody in a dose-dependent manner,suggesting that the cancerous Ig-Fc receptor interaction inhibits natural killer cell(or NK cell)effector function.The prevalent expression of Ig in human carcinomas and its capacity to promote growth and inhibit immunity might have important implications in growth regulation and targeted therapy for human cancers.
基金supported by the National High Technology Research and Development Program(863)of China(no.2006AA02A404)the National Nature Science Foundation of China(nos.30471968 and 30772465)the CMB Educational Thrust Project(04-799).
文摘Accumulating evidence has shown that immunoglobulin(Ig)is‘unexpectedly’expressed by epithelial cancer cells and that it can promote tumor growth.The main purpose of this study was to explore the components of the cancerous Ig and its possible function.The presence of cancerous Ig in the Golgi apparatus was confirmed by immunofluorescence,indirectly suggesting that the cancerous Ig was processed and packaged in cancer cells.Western blot analysis and ELISA results indicated that cancer cells produced membrane Ig and secreted Ig into the supernatant fraction.The cancerous Ig consists of an a heavy chain and a k light chain.Finally,by analyzing the Ig components pulled down by protein A beads,the cancerous Ig was found to be structurally distinct from normal Ig.The cancerous Ig was truncated or aberrant.Although the underlying mechanism that causes the abnormalities has not been determined,our current discoveries strengthen our previous findings and promise fruitful future explorations.
基金supported by the National Natural Science Foundation of China(No.51721091).
文摘In this work,the lamellar structural evolution and microvoids variations of βpolypropylene(β-PP)during the processing of two different stretching methods,sequential biaxial stretching and simultaneous biaxial stretching,were investigated in detail.It was found that different stretching methods led to significantly different lamellae deformation modes,and the microporous membranes obtained from the simultaneous biaxial stretching exhibited better mechanical properties.For the sequential biaxial stretching,abundant coarse fibers originated from the tight accumulation of the lamellae parallel to the longitudinal stretching direction,whereas the lamellae perpendicular to the stretching direction were easily deformed and separated.Those coarse fibers were difficult to be separated to form micropores during the subsequent transverse stretching process,resulting in a poor micropores distribution.However,for the simultaneous biaxial stretching,theβcrystal had the same deformation mode,that is,the lamellae distributed in different directions were all destroyed,forming abundant microvoids and little coarse fibers.
文摘Immunoglobulins (Igs) are known to be synthesized and secreted only by B lymphocytes. Class switch recombination (CSR) is a key event that enables B cells to express Igs, and one of the crucial steps for CSR initiation is the germline transcription of Iggenes. Surprisingly, recent studies have demonstrated that the Iggenes are also expressed in some epithelial cancer cells; however, the mechanisms underlying how cancer cells initiate CSR and express Igs are still unknown. In this study, we confirmed that the Ig la I promoter in cancer cell lines was activated by the Ets- 1 transcription factor, and the activity of the Ig la I promoter and ig lal-C^l germiine transcription were attenuated after knockdown of Ets-1 by specific small interfering RNAs (siRNA). Furthermore, the expression of Ets-1 and Iga heavy chain in cancer cells was dose dependently upregulated by TGF-I^I. These results indicate that activation of the Ig lal promoter by the transcriotion factor Ets-1 is a critical Dathwav and orovides a novel mechanism for le exoression in non-B cell cancers.
基金supported by the National Science Fund for Distinguished Young Scholars(Grant No.20925520).
文摘This paper reports a novel method to detect human leukemic lymphoblasts(CCRF-CEM cells).While the aptamer of the cancer cells was employed as the recognition element to target cancer cells,peroxidaseactive DNAzyme was used as the sensing element to produce catalysis-induced colorimetric signals.The elegant architecture integrating the aptamer and DNAzyme made it feasible to detect cancer cells easily and rapidly by the color change of the substrate for DNAzyme.Experimental results showed that 500 cells can well indicate the cancer,while as control,250,000 Islet Island Beta cells only show tiny signals,suggesting that the method proposed in this paper has considerable sensitivity and selectivity.Furthermore,since it does not require expensive apparatus,or modification or label of DNA chains,the method we present here is also costeffective and conveniently operated,implying potential applications in future cancer diagnosis.
基金supported by the National Natural Science Foundation of China(81430064,81602402,and 81874172)the College Students’Innovation Project of Central South University(2018zzts230).
文摘Latent membrane protein 1(LMP1)is a major Epstein–Barr virus(EBV)-encoded oncoprotein involved in latency infection that regulates mitochondrial functions to facilitate cell survival.Recently,mitochondrial fission has been demonstrated as a crucial mechanism in oncovirus-mediated carcinogenesis.Mitochondrial dynamin-related protein 1(Drp1)-mediated mitochondrial fission has an impact on the chemoresistance of cancers.However,the mechanism by which oncogenic stress promotes mitochondrial fission,potentially contributing to tumorigenesis,is not entirely understood.The role of Drp1 in the oncogenesis and prognosis of EBV-LMP1-positive nasopharyngeal carcinoma(NPC)was determined in our study.We show that EBV-LMP1 exhibits a new function in remodeling mitochondrial morphology by activating Drp1.A high level of p-Drp1(Ser616)or a low level of p-Drp1(Ser637)correlates with poor overall survival and disease-free survival.Furthermore,the protein level of p-Drp1(Ser616)is related to the clinical stage(TNM stage)of NPC.Targeting Drp1 impairs mitochondrial function and induces cell death in LMP1-positive NPC cells.In addition,EBV-LMP1 regulates Drp1 through two oncogenic signaling axes,AMPK and cyclin B1/Cdk1,which promote cell survival and cisplatin resistance in NPC.Our findings provide novel insight into the role of EBV-LMP1-driven mitochondrial fission in regulating Drp1 phosphorylation at serine 616 and serine 637.Disruption of Drp1 could be a promising therapeutic strategy for LMP1-positive NPC.
基金The National Natural Science Foundation of China(81672991 and 81874139[S.L.],81672787[Y.T.],81672308[X.W.])the National Basic Research Program of China(2015CB553903[Y.T.])supported this study.
文摘Cancer stem cells(CSCs)exhibit highly aggressive and metastatic features and resistance to chemotherapy and radiotherapy.Aryl hydrocarbon receptor(AhR)expression varies among non-small cell lung cancers(NSCLCs),and the mechanisms that support abnormal AhR expression in CSCs remain elusive.Here,we identified ubiquitin carboxyl terminal hydrolase L3(UCHL3),a DUB enzyme in the UCH protease family,as a bona fide deubiquitylase of the AhR in NSCLC.UCHL3 was shown to interact with,deubiquitylate,and stabilize AhR in a manner dependent on its deubiquitylation activity.Moreover,we showed that UCHL3 promotes the stem-like characteristics and potent tumorigenic capacity of NSCLC cells.UCHL3 increased AhR stability and the binding of AhR to the promoter regions of the“stemness”genes ATP-binding cassette subfamily G member 2(ABCG2),KLF4,and c-Myc.Depletion of UCHL3 markedly downregulated the“stemness”genes ABCG2,KLF4,and c-Myc,leading to the loss of selfrenewal and tumorigenesis in NSCLCs.Furthermore,the UCHL3 inhibitor TCID induced AhR degradation and exhibited significantly attenuated efficacy in NSCLC cells with stem cell-like properties.Additionally,UCHL3 was shown to indicate poor prognosis in patients with lung adenocarcinoma.In general,our results reveal that the UCHL3 deubiquitylase is pivotal for AhR protein stability and a potential target for NSCLC-targeted therapy.
文摘Recently, immunoglobulins (Igs) were unexpectedly found to be expressed in epithelial cancers. Immunoglobulin class switching or class switch recombination (CSR) is a natural biological process that alters a B cell's production of antibodies (immunoglobulins) from one class to another. However, the mechanism of CSR of Iggenes in cancer is still unknown. Here, we confirmed by detecting the hallmark of CSR that the Iga gene in cancer underwent CSR. Then we focused on activation-induced cytidine deaminase (AID), a crucial factor for initiating CSR. Further studies using tumor necrosis factor (TNF)-α stimulation and specific inhibitor of NF-KB revealed that TNF-α could increase AID expression through NF-κB signaling. Finally, we demonstrated that AID could co-localize with protein kinase A and bind to the switching (Sα) region of the Igα gene. Overexpression of AID obviously enhanced Igα heavy chain expression and its binding ability to the Sa region. These findings indicated that TNF-α-induced AID expression is involved with CSR in cancer.
基金This study was supported by the National Natural Science Foundation of China(81430064,81602402,and 81672705,81874172).
文摘Epstein-Barr virus-associated diseases are important global health concerns.As a group I carcinogen,EBV accounts for 1.5%of human malignances,including both epithelial-and lymphatic-originated tumors.Moreover,EBV plays an etiological and pathogenic role in a number of non-neoplastic diseases,and is even involved in multiple autoimmune diseases(SADs).In this review,we summarize and discuss some recent exciting discoveries in EBV research area,which including DNA methylation alterations,metabolic reprogramming,the changes of mitochondria and ubiquitin-proteasome system(UPS),oxidative stress and EBV lytic reactivation,variations in non-coding RNA(ncRNA),radiochemotherapy and immunotherapy.Understanding and learning from this advancement will further confrm the far-reaching and future value of therapeutic strategies in EBV-associated diseases.