BACKGROUND Although thymopoietin(TMPO)has been elucidated to be overexpressed in cancers,its underlying mechanisms are not yet fully understood.AIM To investigate the expression and clinical significance of TMPO in pa...BACKGROUND Although thymopoietin(TMPO)has been elucidated to be overexpressed in cancers,its underlying mechanisms are not yet fully understood.AIM To investigate the expression and clinical significance of TMPO in papillary thyroid carcinoma(PTC).METHODS Databases such as Gene Expression Omnibus,The Cancer Genome Atlas Proand summary receiver operating characteristic curves were plotted to evaluate diagnostic performance.A Gene Set Enrichment Analysis enrichment analysis was conducted to identify TMPO-related signaling pathways.A protein interaction network was constructed to identify hub genes.The impact of TMPO on PTC cell proliferation and the effects of its knockout were analyzed using clustered regularly interspaced short palindromic repeats(CRISPR)knockout screening and the Cancer Cell Line Encyclopedia database.RESULTS The TMPO protein was significantly overexpressed in PTC tissues,primarily localized in the cytoplasm and nuclear membrane.The mRNA level analysis showed mild overexpression of TMPO in PTC tissues,with a certain discriminatory value(area under the curve=0.66).TMPO may promote cancer through involvement in cell adhesion,focal adhesion,leukocyte migration,and multiple cancer-related signaling pathways.Additionally,CRISPR gene knockout experiments confirmed that TMPO knockout significantly inhibited the proliferation of PTC cell lines,indicating its important role in tumor growth.CONCLUSION TMPO is overexpressed in PTC and may serve as a therapeutic target and molecular biomarker for PTC.展开更多
The pen shell(Atrina pectinata) is a large wedge-shaped bivalve, which belongs to family Pinnidae. Due to its large and nutritious adductor muscle, it is the popular seafood with high commercial value in Asia-Pacific ...The pen shell(Atrina pectinata) is a large wedge-shaped bivalve, which belongs to family Pinnidae. Due to its large and nutritious adductor muscle, it is the popular seafood with high commercial value in Asia-Pacific countries. However, limiting genomic and transcriptomic data have hampered its genetic investigations. In this study, the transcriptome of A. pectinata was deeply sequenced using Illumina pair-end sequencing technology. After assembling, a total of 127263 unigenes were obtained. Functional annotation indicated that the highest percentage of unigenes(18.60%) was annotated on GO database, followed by 18.44% on PFAM database and 17.04% on NR database. There were 270 biological pathways matched with those in KEGG database. Furthermore, a total of 23452 potential simple sequence repeats(SSRs) were identified, of them the most abundant type was mono-nucleotide repeats(12902, 55.01%), which was followed by di-nucleotide(8132, 34.68%), tri-nucleotide(2010, 8.57%), tetra-nucleotide(401, 1.71%), and penta-nucleotide(7, 0.03%) repeats. Sixty SSRs were selected for validating and developing genic SSR markers, of them 23 showed polymorphism in a cultured population with the average observed and expected heterozygosities of 0.412 and 0.579, respectively. In this study, we established the first comprehensive transcript dataset of A. pectinata genes. Our results demonstrated that RNA-Seq is a fast and cost-effective method for genic SSR development in non-model species.展开更多
BACKGROUND The prevalence of colorectal cancer(CRC)in younger people is increasing.Despite advances in precision medicine,the challenges of drug resistance and high costs persist.Nitidine chloride(NC)has pharmacologic...BACKGROUND The prevalence of colorectal cancer(CRC)in younger people is increasing.Despite advances in precision medicine,the challenges of drug resistance and high costs persist.Nitidine chloride(NC)has pharmacological potential,and kinesin family member 20A(KIF20A)is overexpressed in various tumors;however,their interaction in CRC remains unexplored.AIM To investigate the KIF20A expression characteristics in CRC cells and determine whether it is a potential target gene for NC in inhibiting CRC treatment.METHODS Single-cell RNA sequencing(scRNA-seq),spatial transcriptomics,and mRNA expression profiling were used to analyze KIF20A expression in CRC cells.Immunohistochemical staining was used to verify KIF20A expression in 416 clinical samples(208 CRC tissue samples and 208 noncancerous control tissue samples).Clustered regularly interspaced short palindromic repeats(CRISPR)technology was used to evaluate the impact of knocking out KIF20A on CRC cell growth.Molecular docking was applied to analyze NC–KIF20A binding.Finally,RNA sequencing and functional enrichment analysis were performed to explore the mechanism of action of NC in CRC cells.RESULTS Treating HCT116 cells with NC was found to significantly downregulate KIF20A(P<0.05),and the molecular docking analysis revealed high-affinity binding between NC and KIF20A(binding energy=-9.6 kcal/mol).The scRNA-seq,spatial transcriptomics,and mRNA expression profiling results confirmed the significantly high expression of KIF20A in CRC tissues(standardized mean difference=1.33,95%confidence interval:0.885-1.77,summary receiver operating characteristic curve area=0.94).The immunohistochemical analysis of the clinical samples showed high KIF20A expression in the CRC tissues(P<0.05),with significant correlation between the level of expression and gender,tumor size,and tumor grade(P<0.05).Knocking out KIF20A significantly inhibited the growth of various CRC cell lines(CRISPR score<-0.3).The functional enrichment analysis indicated that NC may inhibit CRC by disrupting several biological processes,such as mitotic nuclear division,chromosome segregation,and microtubule binding.CONCLUSION Our results indicate that NC binds to KIF20A with high affinity and downregulates its expression in CRC cells,leading to reduced proliferation.Hence,NC has promise as a therapeutic agent in the treatment of CRC,and targeting KIF20A also has potential as a therapeutic strategy.Further KIF20A knockout studies are needed to confirm the binding specificity and mechanistic roles of NC in CRC.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)remains a lethal malignancy due to its molecular complexity and chemoresistance.Rac family small GTPase 3(RAC3),a tumorigenic GTPase understudied in HCC,drives recurrence via E2...BACKGROUND Hepatocellular carcinoma(HCC)remains a lethal malignancy due to its molecular complexity and chemoresistance.Rac family small GTPase 3(RAC3),a tumorigenic GTPase understudied in HCC,drives recurrence via E2F transcription factor 1(E2F1)-mediated transcriptional activation.This study integrates multiomics and clustered regularly interspaced short palindromic repeats(CRISPR)screening to delineate RAC3’s roles.RAC3 overexpression correlates with advanced HCC and patient age,while its knockout suppresses proliferation.Mechanistically,RAC3 dysregulates cell-cycle checkpoints through E2F1 binding.Pharmacological RAC3 inhibition disrupts tumor growth and synergizes with chemotherapy to overcome resistance.AIM To explore RAC3’s expression,clinical links,and HCC mechanisms via multiomics and functional genomics.METHODS Multiomic integration of The Cancer Genome Atlas(TCGA),Gene Expression Omnibus,and Genotype-Tissue Expression datasets was performed to analyze RAC3 mRNA expression.Immunohistochemistry quantified RAC3 protein in 108 HCC/adjacent tissue pairs.Kaplan–Meier/Cox regression assessed prognostic significance using TCGA data.CRISPR screening validated RAC3’s necessity for HCC proliferation.Functional enrichment identified associated pathways;hTFtarget/JASPAR predicted transcription factors,validated via chromatin immunoprecipitation sequencing(ChIP-seq).RESULTS RAC3 exhibited significant mRNA and protein overexpression in HCC tissues,which was correlated with advanced tumor stages and reduced overall survival rates(hazard ratio=1.82,95%CI:1.31–2.53).Genetic ablation of RAC3 suppressed HCC cell proliferation across 16 cell lines.Pathway analysis revealed RAC3’s predominant involvement in cell-cycle regulation,DNA replication,and nucleocytoplasmic transport.Mechanistic investigations identified E2F1 as a pivotal upstream transcriptional regulator,and ChIP-seq analysis validated its direct binding to the RAC3 promoter region.These findings suggest that RAC3 drives HCC progression through E2F1-mediated cell-cycle dysregulation.CONCLUSION This study identified RAC3 as a key HCC oncogenic driver;its overexpression links to poor prognosis/resistance.Targeting the RAC3/E2F1 axis offers a new therapy,which highlights RAC3 as a biomarker/target.展开更多
基金Supported by Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z-A20220521Guangxi Higher Education Undergraduate Teaching Reform Project,No.2022JGA147The National College Students’Innovation and Entrepreneurship Training Program,No.202310598042.
文摘BACKGROUND Although thymopoietin(TMPO)has been elucidated to be overexpressed in cancers,its underlying mechanisms are not yet fully understood.AIM To investigate the expression and clinical significance of TMPO in papillary thyroid carcinoma(PTC).METHODS Databases such as Gene Expression Omnibus,The Cancer Genome Atlas Proand summary receiver operating characteristic curves were plotted to evaluate diagnostic performance.A Gene Set Enrichment Analysis enrichment analysis was conducted to identify TMPO-related signaling pathways.A protein interaction network was constructed to identify hub genes.The impact of TMPO on PTC cell proliferation and the effects of its knockout were analyzed using clustered regularly interspaced short palindromic repeats(CRISPR)knockout screening and the Cancer Cell Line Encyclopedia database.RESULTS The TMPO protein was significantly overexpressed in PTC tissues,primarily localized in the cytoplasm and nuclear membrane.The mRNA level analysis showed mild overexpression of TMPO in PTC tissues,with a certain discriminatory value(area under the curve=0.66).TMPO may promote cancer through involvement in cell adhesion,focal adhesion,leukocyte migration,and multiple cancer-related signaling pathways.Additionally,CRISPR gene knockout experiments confirmed that TMPO knockout significantly inhibited the proliferation of PTC cell lines,indicating its important role in tumor growth.CONCLUSION TMPO is overexpressed in PTC and may serve as a therapeutic target and molecular biomarker for PTC.
基金the grants from Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, P. R. China (No. 2016LMFS-B02)the Key Research and Development Program of Shandong Province (No. 2016GSF115012)+1 种基金Basic Scientific Research Fund of YSFRI (No. 2060302201516054)Natural Science Foundation of Shandong Province (No. ZR2016 CQ32)
文摘The pen shell(Atrina pectinata) is a large wedge-shaped bivalve, which belongs to family Pinnidae. Due to its large and nutritious adductor muscle, it is the popular seafood with high commercial value in Asia-Pacific countries. However, limiting genomic and transcriptomic data have hampered its genetic investigations. In this study, the transcriptome of A. pectinata was deeply sequenced using Illumina pair-end sequencing technology. After assembling, a total of 127263 unigenes were obtained. Functional annotation indicated that the highest percentage of unigenes(18.60%) was annotated on GO database, followed by 18.44% on PFAM database and 17.04% on NR database. There were 270 biological pathways matched with those in KEGG database. Furthermore, a total of 23452 potential simple sequence repeats(SSRs) were identified, of them the most abundant type was mono-nucleotide repeats(12902, 55.01%), which was followed by di-nucleotide(8132, 34.68%), tri-nucleotide(2010, 8.57%), tetra-nucleotide(401, 1.71%), and penta-nucleotide(7, 0.03%) repeats. Sixty SSRs were selected for validating and developing genic SSR markers, of them 23 showed polymorphism in a cultured population with the average observed and expected heterozygosities of 0.412 and 0.579, respectively. In this study, we established the first comprehensive transcript dataset of A. pectinata genes. Our results demonstrated that RNA-Seq is a fast and cost-effective method for genic SSR development in non-model species.
基金Supported by the Promoting Project of Basic Capacity for Young and Middle-aged University Teachers in Guangxi,No.2025KY0164Youth Science Foundation of Guangxi Medical University,No.GXMUYSF202423Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z-A20220415 and No.Z20210442.
文摘BACKGROUND The prevalence of colorectal cancer(CRC)in younger people is increasing.Despite advances in precision medicine,the challenges of drug resistance and high costs persist.Nitidine chloride(NC)has pharmacological potential,and kinesin family member 20A(KIF20A)is overexpressed in various tumors;however,their interaction in CRC remains unexplored.AIM To investigate the KIF20A expression characteristics in CRC cells and determine whether it is a potential target gene for NC in inhibiting CRC treatment.METHODS Single-cell RNA sequencing(scRNA-seq),spatial transcriptomics,and mRNA expression profiling were used to analyze KIF20A expression in CRC cells.Immunohistochemical staining was used to verify KIF20A expression in 416 clinical samples(208 CRC tissue samples and 208 noncancerous control tissue samples).Clustered regularly interspaced short palindromic repeats(CRISPR)technology was used to evaluate the impact of knocking out KIF20A on CRC cell growth.Molecular docking was applied to analyze NC–KIF20A binding.Finally,RNA sequencing and functional enrichment analysis were performed to explore the mechanism of action of NC in CRC cells.RESULTS Treating HCT116 cells with NC was found to significantly downregulate KIF20A(P<0.05),and the molecular docking analysis revealed high-affinity binding between NC and KIF20A(binding energy=-9.6 kcal/mol).The scRNA-seq,spatial transcriptomics,and mRNA expression profiling results confirmed the significantly high expression of KIF20A in CRC tissues(standardized mean difference=1.33,95%confidence interval:0.885-1.77,summary receiver operating characteristic curve area=0.94).The immunohistochemical analysis of the clinical samples showed high KIF20A expression in the CRC tissues(P<0.05),with significant correlation between the level of expression and gender,tumor size,and tumor grade(P<0.05).Knocking out KIF20A significantly inhibited the growth of various CRC cell lines(CRISPR score<-0.3).The functional enrichment analysis indicated that NC may inhibit CRC by disrupting several biological processes,such as mitotic nuclear division,chromosome segregation,and microtubule binding.CONCLUSION Our results indicate that NC binds to KIF20A with high affinity and downregulates its expression in CRC cells,leading to reduced proliferation.Hence,NC has promise as a therapeutic agent in the treatment of CRC,and targeting KIF20A also has potential as a therapeutic strategy.Further KIF20A knockout studies are needed to confirm the binding specificity and mechanistic roles of NC in CRC.
基金Supported by National Natural Science Foundation of China,No.82260581.
文摘BACKGROUND Hepatocellular carcinoma(HCC)remains a lethal malignancy due to its molecular complexity and chemoresistance.Rac family small GTPase 3(RAC3),a tumorigenic GTPase understudied in HCC,drives recurrence via E2F transcription factor 1(E2F1)-mediated transcriptional activation.This study integrates multiomics and clustered regularly interspaced short palindromic repeats(CRISPR)screening to delineate RAC3’s roles.RAC3 overexpression correlates with advanced HCC and patient age,while its knockout suppresses proliferation.Mechanistically,RAC3 dysregulates cell-cycle checkpoints through E2F1 binding.Pharmacological RAC3 inhibition disrupts tumor growth and synergizes with chemotherapy to overcome resistance.AIM To explore RAC3’s expression,clinical links,and HCC mechanisms via multiomics and functional genomics.METHODS Multiomic integration of The Cancer Genome Atlas(TCGA),Gene Expression Omnibus,and Genotype-Tissue Expression datasets was performed to analyze RAC3 mRNA expression.Immunohistochemistry quantified RAC3 protein in 108 HCC/adjacent tissue pairs.Kaplan–Meier/Cox regression assessed prognostic significance using TCGA data.CRISPR screening validated RAC3’s necessity for HCC proliferation.Functional enrichment identified associated pathways;hTFtarget/JASPAR predicted transcription factors,validated via chromatin immunoprecipitation sequencing(ChIP-seq).RESULTS RAC3 exhibited significant mRNA and protein overexpression in HCC tissues,which was correlated with advanced tumor stages and reduced overall survival rates(hazard ratio=1.82,95%CI:1.31–2.53).Genetic ablation of RAC3 suppressed HCC cell proliferation across 16 cell lines.Pathway analysis revealed RAC3’s predominant involvement in cell-cycle regulation,DNA replication,and nucleocytoplasmic transport.Mechanistic investigations identified E2F1 as a pivotal upstream transcriptional regulator,and ChIP-seq analysis validated its direct binding to the RAC3 promoter region.These findings suggest that RAC3 drives HCC progression through E2F1-mediated cell-cycle dysregulation.CONCLUSION This study identified RAC3 as a key HCC oncogenic driver;its overexpression links to poor prognosis/resistance.Targeting the RAC3/E2F1 axis offers a new therapy,which highlights RAC3 as a biomarker/target.
