Background: Fusobacterium nucleatum can cause opportunistic and chronic infections and has recently been shown to be involved in colorectal cancer. However, the specific mechanism by which F. nucleatum induces colorect...Background: Fusobacterium nucleatum can cause opportunistic and chronic infections and has recently been shown to be involved in colorectal cancer. However, the specific mechanism by which F. nucleatum induces colorectal carcinoma remains unclear. Methods: We downloaded the GSE110223, GSE110224, GSE113513 and GSE122183 microarray datasets from the Gene Expression Omnibus (GEO) database. Identification of differentially expressed genes (DEGs) related to F. nucleatum in CRC by overlapping data sets was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome pathway (KEGG) analyses were used for enrichment analysis. Moreover, Cytoscape software constructed a protein-protein interaction (PPI) network of differentially expressed genes. Finally, western blot and RT-qPCR analysis identified the relative protein and mRNA expression of hub genes in the cell model. Results: In total, 118 DEGs in F. nucleatum-associated CRC were screened from nonoverlapping microarray data, among which 20 upregulated and 98 downregulated DEGs were identified. The 118 DEGs were significantly correlated with diverse functions and pathways. The hub gene MUC1 had higher centrality scores in the PPI network, and the top 5 closely interacting hub genes, SLC7A11, AGR2, KRT18, CARTPT and TSPYL5, were identified. Conclusion: Our evidence suggests that the identified DEGs associated with F. nucleatum enhance our comprehension of the molecular Mechanisms underlying the tumorigenesis and development of CRC and might be used as molecular targets and diagnostic biomarkers for the treatment of CRC.展开更多
Fusobacterium nucleatum(F.nucleatum)is a Gram-negative anaerobic bacterium that plays a key role in the development of oral inflammation,such as periodontitis and gingivitis.In the last 10 years,F.nucleatum has been i...Fusobacterium nucleatum(F.nucleatum)is a Gram-negative anaerobic bacterium that plays a key role in the development of oral inflammation,such as periodontitis and gingivitis.In the last 10 years,F.nucleatum has been identified as a prevalent bacterium associated with colorectal adenocarcinoma and has also been linked to cancer progression,metastasis and poor disease outcome.While the role of F.nucleatum in colon carcinogenesis has been intensively studied,its role in gastric carcinogenesis is still poorly understood.Although Helicobacter pylori infection has histo-rically been recognized as the strongest risk factor for the development of gastric cancer(GC),with recent advances in DNA sequencing technology,other members of the gastric microbial community,and F.nucleatum in particular,have received increasing attention.In this review,we summarize the existing knowledge on the involvement of F.nucleatum in gastric carcinogenesis and address the potential translational and clinical significance of F.nucleatum in GC.展开更多
The morbidity and mortality of gastrointestinal(GI)malignancies are among the highest in the world,posing a serious threat to human health.Because of the insidious onset of the cancer,it is difficult for patients to b...The morbidity and mortality of gastrointestinal(GI)malignancies are among the highest in the world,posing a serious threat to human health.Because of the insidious onset of the cancer,it is difficult for patients to be diagnosed at an early stage,and it rapidly progresses to an advanced stage,resulting in poor treatment and prognosis.Fusobacterium nucleatum(F.nucleatum)is a gram-negative,sporefree anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal,esophageal,gastric,and pancreatic cancers via various intricate mechanisms.Recent development in novel research suggests that F.nucleatum may function as a biomarker in GI malignancies.Detecting the abundance of F.nucleatum in stool,saliva,and serum samples of patients may aid in the diagnosis,risk assessment,and prognosis monitoring of GI malignancies.This editorial systematically describes the biological roles and mechanisms of F.nucleatum in GI malignancies focusing on the application of F.nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F.nucleatum and GI tumors-related research.展开更多
Fusobacterium nucleatum is an anaerobic, commensal, gram-negative oral bacterium that is carcinogenic and causes a wide range of human diseases. The present study focused on the analysis of the hypothetical protein, H...Fusobacterium nucleatum is an anaerobic, commensal, gram-negative oral bacterium that is carcinogenic and causes a wide range of human diseases. The present study focused on the analysis of the hypothetical protein, HMPREF3221_01179, derived from F. nucleatum strain MJR7757B, employing various computational methods to anticipate both its structure and functional characteristics. NCBI conserved domain analysis, NCBI BLASTp and MEGA Phylogenetic tree study characterize the target protein as an outer membrane efflux protein (ToIC family) which facilitate the bacterial transmembrane transport. With a molecular weight of 52120.02 Da, an isoelectric point (pI) of 8.33, and an instability index of 29.47, the protein is anticipated to exhibit good solubility in the extracellular space and crucial stability for pharmaceutical applications. The protein’s structure meets quality standards during the construction and refinement of its 3D model. The efflux inhibitor Arginine beta-naphthylamide exhibits a significant binding affinity (-7.1 kcal/mol) to the binding site of the target protein. The in-silico analysis improves the understanding of the protein and facilitates future investigations into therapeutic medication.展开更多
BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignant tumors globally.Recent reports suggest that Fusobacterium nucleatum(F.nucleatum)contributes to the initiation,progression,and prognosis of CRC....BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignant tumors globally.Recent reports suggest that Fusobacterium nucleatum(F.nucleatum)contributes to the initiation,progression,and prognosis of CRC.Butyrate,a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber,is known to inhibit various cancers.This study is designed to explore whether F.nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid.AIM To investigate the mechanism by which F.nucleatum affects CRC occurrence and development.METHODS Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F.nucleatum.Additionally,DLD-1 and HCT116 cell lines were exposed to sodium butyrate(NaB)and F.nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function.RESULTS Our research indicates that the prevalence of F.nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts,while the prevalence of butyrate-producing bacteria is notably lower.In mice colonized with F.nucleatum,the population of butyrate-producing bacteria decreased,resulting in altered levels of butyric acid,a key intestinal metabolite of butyrate.Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells.Consequently,this leads to modulated production of adenosine triphosphate and reactive oxygen species,thereby inhibiting cancer cell prolif-eration.Additionally,NaB triggers the adenosine monophosphate-activated protein kinase(AMPK)signaling pathway,blocks the cell cycle in HCT116 and DLD-1 cells,and curtails the proliferation of CRC cells.The combined presence of F.nucleatum and NaB attenuated the effects of the latter.By employing small interfering RNA to suppress AMPK,it was demonstrated that AMPK is essential for NaB’s inhibition of CRC cell proliferation.CONCLUSION F.nucleatum can promote cancer progression through its inhibitory effect on butyric acid,via the AMPK signaling pathway.展开更多
目的:探讨血清抗着丝粒蛋白F抗体(anti-centromere protein F antibody,anti-CENPF)在乳腺癌中的临床价值。方法:收集100例初诊乳腺癌(breast cancer,BC)患者、40例乳腺良性疾病(non breast cancer,non-BC)患者和40名健康体检者(healthy...目的:探讨血清抗着丝粒蛋白F抗体(anti-centromere protein F antibody,anti-CENPF)在乳腺癌中的临床价值。方法:收集100例初诊乳腺癌(breast cancer,BC)患者、40例乳腺良性疾病(non breast cancer,non-BC)患者和40名健康体检者(healthy control,HC)血清,采用酶联免疫吸附试验检测血清中的anti-CENPF水平,同时化学发光法测定血清糖类抗原153(carbohydrate antigen 153,CA153)的水平。结果:BC组血清anti-CENPF水平高于non-BC组和HC组,差异有统计学意义(P<0.05)。anti-CENPF和CA153诊断乳腺癌中的曲线下面积(area under the curve,AUC)分别为0.714和0.672,两者联合检测的AUC为0.739。有淋巴结转移、远处转移或者人表皮生长因子受体2(human epidermal growth factor receptor-2,HER-2)阴性的乳腺癌患者血清anti-CENPF浓度明显升高(P<0.05)。不同肿瘤大小、临床分期、分子分型乳腺癌患者血清anti-CENPF水平比较,差异有统计学意义(P<0.05)。组间比较显示Ⅳ期和Ⅲ期血清anti-CENPF浓度高于Ⅰ期和Ⅱ期,HER-2过表达型、Luminal B型血清anti-CENPF水平低于三阴性乳腺癌(triple negative breast cancer,TNBC)患者。雌激素受体(receptors estrogen,ER)阳性的乳腺癌患者中,HER-2阴性组的anti-CENPF浓度高于HER-2阳性组,差异有统计学意义(P=0.026)。结论:血清antiCENPF在乳腺癌的诊断、临床分期及分子分型中发挥了重要作用,其水平可能与乳腺癌预后呈负相关,有望成为乳腺癌潜在的疾病标志物。展开更多
文摘Background: Fusobacterium nucleatum can cause opportunistic and chronic infections and has recently been shown to be involved in colorectal cancer. However, the specific mechanism by which F. nucleatum induces colorectal carcinoma remains unclear. Methods: We downloaded the GSE110223, GSE110224, GSE113513 and GSE122183 microarray datasets from the Gene Expression Omnibus (GEO) database. Identification of differentially expressed genes (DEGs) related to F. nucleatum in CRC by overlapping data sets was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome pathway (KEGG) analyses were used for enrichment analysis. Moreover, Cytoscape software constructed a protein-protein interaction (PPI) network of differentially expressed genes. Finally, western blot and RT-qPCR analysis identified the relative protein and mRNA expression of hub genes in the cell model. Results: In total, 118 DEGs in F. nucleatum-associated CRC were screened from nonoverlapping microarray data, among which 20 upregulated and 98 downregulated DEGs were identified. The 118 DEGs were significantly correlated with diverse functions and pathways. The hub gene MUC1 had higher centrality scores in the PPI network, and the top 5 closely interacting hub genes, SLC7A11, AGR2, KRT18, CARTPT and TSPYL5, were identified. Conclusion: Our evidence suggests that the identified DEGs associated with F. nucleatum enhance our comprehension of the molecular Mechanisms underlying the tumorigenesis and development of CRC and might be used as molecular targets and diagnostic biomarkers for the treatment of CRC.
基金Supported by The European Union’s“Horizon Europe Framework Program”Grant Agreement,No.101095359(AIDA project under the call"HORIZON-HLTH-2022-STAYHLTH-02).
文摘Fusobacterium nucleatum(F.nucleatum)is a Gram-negative anaerobic bacterium that plays a key role in the development of oral inflammation,such as periodontitis and gingivitis.In the last 10 years,F.nucleatum has been identified as a prevalent bacterium associated with colorectal adenocarcinoma and has also been linked to cancer progression,metastasis and poor disease outcome.While the role of F.nucleatum in colon carcinogenesis has been intensively studied,its role in gastric carcinogenesis is still poorly understood.Although Helicobacter pylori infection has histo-rically been recognized as the strongest risk factor for the development of gastric cancer(GC),with recent advances in DNA sequencing technology,other members of the gastric microbial community,and F.nucleatum in particular,have received increasing attention.In this review,we summarize the existing knowledge on the involvement of F.nucleatum in gastric carcinogenesis and address the potential translational and clinical significance of F.nucleatum in GC.
基金Supported by the National Natural Science Foundation of China,No.81972005and Taishan Scholar Program of Shandong Province,No.tsqn202306346 and No.tstp20221156.
文摘The morbidity and mortality of gastrointestinal(GI)malignancies are among the highest in the world,posing a serious threat to human health.Because of the insidious onset of the cancer,it is difficult for patients to be diagnosed at an early stage,and it rapidly progresses to an advanced stage,resulting in poor treatment and prognosis.Fusobacterium nucleatum(F.nucleatum)is a gram-negative,sporefree anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal,esophageal,gastric,and pancreatic cancers via various intricate mechanisms.Recent development in novel research suggests that F.nucleatum may function as a biomarker in GI malignancies.Detecting the abundance of F.nucleatum in stool,saliva,and serum samples of patients may aid in the diagnosis,risk assessment,and prognosis monitoring of GI malignancies.This editorial systematically describes the biological roles and mechanisms of F.nucleatum in GI malignancies focusing on the application of F.nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F.nucleatum and GI tumors-related research.
文摘Fusobacterium nucleatum is an anaerobic, commensal, gram-negative oral bacterium that is carcinogenic and causes a wide range of human diseases. The present study focused on the analysis of the hypothetical protein, HMPREF3221_01179, derived from F. nucleatum strain MJR7757B, employing various computational methods to anticipate both its structure and functional characteristics. NCBI conserved domain analysis, NCBI BLASTp and MEGA Phylogenetic tree study characterize the target protein as an outer membrane efflux protein (ToIC family) which facilitate the bacterial transmembrane transport. With a molecular weight of 52120.02 Da, an isoelectric point (pI) of 8.33, and an instability index of 29.47, the protein is anticipated to exhibit good solubility in the extracellular space and crucial stability for pharmaceutical applications. The protein’s structure meets quality standards during the construction and refinement of its 3D model. The efflux inhibitor Arginine beta-naphthylamide exhibits a significant binding affinity (-7.1 kcal/mol) to the binding site of the target protein. The in-silico analysis improves the understanding of the protein and facilitates future investigations into therapeutic medication.
基金Supported by the Key Discipline of Zhejiang Province in Medical Technology(First Class,Category A)and the Health Project of the Science and Technology Department of Wenzhou,No.Y20220029.
文摘BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignant tumors globally.Recent reports suggest that Fusobacterium nucleatum(F.nucleatum)contributes to the initiation,progression,and prognosis of CRC.Butyrate,a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber,is known to inhibit various cancers.This study is designed to explore whether F.nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid.AIM To investigate the mechanism by which F.nucleatum affects CRC occurrence and development.METHODS Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F.nucleatum.Additionally,DLD-1 and HCT116 cell lines were exposed to sodium butyrate(NaB)and F.nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function.RESULTS Our research indicates that the prevalence of F.nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts,while the prevalence of butyrate-producing bacteria is notably lower.In mice colonized with F.nucleatum,the population of butyrate-producing bacteria decreased,resulting in altered levels of butyric acid,a key intestinal metabolite of butyrate.Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells.Consequently,this leads to modulated production of adenosine triphosphate and reactive oxygen species,thereby inhibiting cancer cell prolif-eration.Additionally,NaB triggers the adenosine monophosphate-activated protein kinase(AMPK)signaling pathway,blocks the cell cycle in HCT116 and DLD-1 cells,and curtails the proliferation of CRC cells.The combined presence of F.nucleatum and NaB attenuated the effects of the latter.By employing small interfering RNA to suppress AMPK,it was demonstrated that AMPK is essential for NaB’s inhibition of CRC cell proliferation.CONCLUSION F.nucleatum can promote cancer progression through its inhibitory effect on butyric acid,via the AMPK signaling pathway.
文摘目的:探讨血清抗着丝粒蛋白F抗体(anti-centromere protein F antibody,anti-CENPF)在乳腺癌中的临床价值。方法:收集100例初诊乳腺癌(breast cancer,BC)患者、40例乳腺良性疾病(non breast cancer,non-BC)患者和40名健康体检者(healthy control,HC)血清,采用酶联免疫吸附试验检测血清中的anti-CENPF水平,同时化学发光法测定血清糖类抗原153(carbohydrate antigen 153,CA153)的水平。结果:BC组血清anti-CENPF水平高于non-BC组和HC组,差异有统计学意义(P<0.05)。anti-CENPF和CA153诊断乳腺癌中的曲线下面积(area under the curve,AUC)分别为0.714和0.672,两者联合检测的AUC为0.739。有淋巴结转移、远处转移或者人表皮生长因子受体2(human epidermal growth factor receptor-2,HER-2)阴性的乳腺癌患者血清anti-CENPF浓度明显升高(P<0.05)。不同肿瘤大小、临床分期、分子分型乳腺癌患者血清anti-CENPF水平比较,差异有统计学意义(P<0.05)。组间比较显示Ⅳ期和Ⅲ期血清anti-CENPF浓度高于Ⅰ期和Ⅱ期,HER-2过表达型、Luminal B型血清anti-CENPF水平低于三阴性乳腺癌(triple negative breast cancer,TNBC)患者。雌激素受体(receptors estrogen,ER)阳性的乳腺癌患者中,HER-2阴性组的anti-CENPF浓度高于HER-2阳性组,差异有统计学意义(P=0.026)。结论:血清antiCENPF在乳腺癌的诊断、临床分期及分子分型中发挥了重要作用,其水平可能与乳腺癌预后呈负相关,有望成为乳腺癌潜在的疾病标志物。
