AIM:To investigate the proliferation regulatory effect of cone-rod homeobox(CRX)in retinal pigment epithelium(RPE)and retinoblastoma(RB)cells to explore the potential application and side effect(oncogenic potential)of...AIM:To investigate the proliferation regulatory effect of cone-rod homeobox(CRX)in retinal pigment epithelium(RPE)and retinoblastoma(RB)cells to explore the potential application and side effect(oncogenic potential)of CRXbased gene therapy in RPE-based retinopathies.METHODS:Adult human retinal pigment epithelial(ARPE)-19 and human retinal pigment epithelial(RPE)-1 cells and Y79 RB cell were used in the study.Genetic manipulation was performed by lentivirus-based technology.The cell proliferation was determined by a CellTiter-Glo Reagent.The mRNA and protein levels were determined by quantitative real-time polymerase chain reaction(qPCR)and Western blot assay.The transcriptional activity of the promoter was determined by luciferase reporter gene assay.The bindings between CRX and transcription factor 7(TCF7)promoter as well as TCF7 and the promoters of TCF7 target genes were examined by chromatin immunoprecipitation(ChIP)assay.The transcription of the TCF7 was determined by a modified nuclear run-on assay.RESULTS:CRX overexpression and knockdown significantly increased(n=3,P<0.05 in all the cells)and decreased(n=3,P<0.01 in all the cells)the proliferation of RPE and RB cells.CRX overexpression and knockdown significantly increased and deceased the mRNA levels of Wnt signaling target genes[including MYC proto-oncogene(MYC),JUN,FOS like 1(FOSL1),CCND1,cyclin D2(CCND2),cyclin D3(CCND3),cellular communication network factor 4(CCN4),peroxisome proliferator activated receptor delta(PPARD),and matrix metallopeptidase 7(MMP7)]and the luciferase activity driven by the Wnt signaling transcription factor(TCF7).TCF7 overexpression and knockdown significantly increased and decreased the proliferation of RPE and RB cells and depletion of TCF7 significantly abolished the stimulatory effect of CRX on the proliferation of RPE and RB cells.CRX overexpression and knockdown significantly increased and decreased the mRNA level of TCF7 and the promoter of TCF7 was significantly immunoprecipitated by CRX antibody.CONCLUSION:CRX transcriptionally activates TCF7 to promote the proliferation of RPE and RB cells in vitro.CRX is a potential target for RPE-based regenerative medicine.The potential risk of this strategy,tumorigenic potential,should be considered.展开更多
Homeobox(HOX)C9,a member of the HOX family,is an important transcription factor,and it plays a significant role in various biological processes.This family of genes is highly valued for their essential roles in establ...Homeobox(HOX)C9,a member of the HOX family,is an important transcription factor,and it plays a significant role in various biological processes.This family of genes is highly valued for their essential roles in establishing and maintaining the body axis during embryonic development and adult tissues.Further,HOXC9 plays a central role in neuronal differentiation,angiogenesis,and adipose distribution,which are essential for the development of the nervous system,maturation of tissues and organs,and maintenance of energy balance and metabolic health.Recent research has found that abnormal HOXC9 expression is closely associated with the development and progression of various tumor types.The HOXC9 expression level can be an indicator of tumor prognosis.Therefore,elucidating the association between HOXC9 expression and its regulatory mechanisms and tumorigenesis can provide novel insights on the diagnosis and treatment of patients with cancer.展开更多
The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis acro...The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis across various organisms,including humans.Comprising six distinct members,from SIX1 to SIX6,each member contributes uniquely to the development and differentiation of diverse tissues and organs,underscoring the versatility of the SIX family.Dysregulation or mutations in SIX genes have been implicated in a spectrum of developmental disorders,as well as in tumor initiation and progression,highlighting their pivotal role in maintaining normal developmental trajectories and cellular functions.Efforts to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor development.While the development of inhibitors targeting this gene family is still in its early stages,the significant potential of such interventions holds promise for future therapeutic advances.Therefore,this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers,focusing on its critical role in normal organ development and its implications in gastrointestinal cancers,including gastric,pancreatic,colorectal cancer,and hepatocellular carcinomas.In conclusion,this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis,prognosis,and treatment of gastrointestinal cancers.展开更多
BACKGROUND The distal-less homeobox(DLX)gene family plays an important role in the development of several tumors.However,the expression pattern,prognostic and diagnostic value,possible regulatory mechanisms,and the re...BACKGROUND The distal-less homeobox(DLX)gene family plays an important role in the development of several tumors.However,the expression pattern,prognostic and diagnostic value,possible regulatory mechanisms,and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported.AIM We aimed to comprehensively analyze the biological role of the DLX gene family in the pathogenesis of colon cancer.METHODS Colon cancer tissue and normal colon tissue samples were collected from the Cancer Genome Atlas and Gene Expression Omnibus databases.Wilcoxon rank sum test and t-test were used to assess DLX gene family expression between colon cancer tissue and unpaired normal colon tissue.cBioPortal was used to analyze DLX gene family variants.R software was used to analyze DLX gene expression in colon cancer and the relationship between DLX gene family expression and clinical features and correlation heat map.The survival package and Cox regression module were used to assess the prognostic value of the DLX gene family.The pROC package was used to analyze the diagnostic value of the DLX gene family.R software was used to analyze the possible regulatory mechanisms of DLX gene family members and related genes.The GSVA package was used to analyze the relationship between the DLX gene family and immune infiltration.The ggplot2,the survminer package,and the clusterProfiler package were used for visualization.RESULTS DLX1/2/3/4/5 were significantly aberrantly expressed in colon cancer patients.The expression of DLX genes were associated with M stage,pathologic stage,primary therapy outcome,residual tumor,lymphatic invasion,T stage,N stage,age,perineural invasion,and history of colon polyps.DLX5 was independently correlated with the prognosis of colon cancer in multivariate analysis.DLX1/2/3/4/5/6 were involved in the development and progression of colon cancer by participating in immune infiltration and associated pathways,including the Hippo signaling pathway,the Wnt signaling pathway,several signaling pathways regulating the pluripotency of stem cells,and Staphylococcus aureus infection.CONCLUSION The results of this study suggest a possible role for the DLX gene family as potential diagnostic or prognostic biomarkers and therapeutic targets in colon cancer.展开更多
BACKGROUND It is unclear that paired-related homeobox 1(PRRX1)induces epithelialmesenchymal transition(EMT)in oesophageal cancer and the specific function of PRRX1 in oesophageal cancer metastasis.AIM To assess the si...BACKGROUND It is unclear that paired-related homeobox 1(PRRX1)induces epithelialmesenchymal transition(EMT)in oesophageal cancer and the specific function of PRRX1 in oesophageal cancer metastasis.AIM To assess the signicance of PRRX1 expression and investigate the mechanism of EMT in oesophageal cancer metastasis.METHODS Detect the expression of PRRX1 by immunohistochemistry in oesophageal tumour tissues and adjacent normal oesophageal tissues;the PRRX1 short hairpin RNA(shRNA)or blank vector lentiviral gene delivery system was transfected into cells;cell proliferation assay,soft agar colony formation assays,cell invasion and migration assays and animal studies were used to observe cells biological characteristics In vitro and in vivo;XAV939 and LiCl were used to alter the activity of Wnt/β-catenin pathway.Immunofluorescence staining and western blot analysis were used to detect protein expression of EMT markers and Wnt/β-catenin pathway.RESULTS PRRX1 is expressed at high levels in oesophageal cancer specimens and is closely related to tumour metastasis in patients with oesophageal cancer.Regulation of PRRX1 expression might exert obvious effects on cell proliferation,especially the migration and invasion of oesophageal cancer cells.Moreover,silencing PRRX1 expression using a shRNA produced the opposite effects.In addition,when PRRX1 was overexpressed,inhibition of the Wnt/β-catenin pathway with XAV939 negated the effect of PRRX1 on EMT,whereas when PRRX1 was downregulated,activation of the Wnt/β-catenin pathway with LiCl impaired the effect on EMT.CONCLUSION PRRX1 is upregulated in oesophageal cancer is closely correlated with cancer metastasis.Additionally,PRRX1 induces EMT in oesophageal cancer metastasis through activation of Wnt/β-catenin signalling.展开更多
目的本研究旨在阐明具有放射基因组特征的基于CT图像的活检以预测非小细胞肺癌(NSCLC)患者仅同源域蛋白同源盒(homeodomain-only protein homeobox,HOPX)基因表达状态和预后。方法根据HOPX的表达将患者标记为HOPX阴性或阳性,并将其分为...目的本研究旨在阐明具有放射基因组特征的基于CT图像的活检以预测非小细胞肺癌(NSCLC)患者仅同源域蛋白同源盒(homeodomain-only protein homeobox,HOPX)基因表达状态和预后。方法根据HOPX的表达将患者标记为HOPX阴性或阳性,并将其分为训练数据集(n=92)和测试数据集(n=24)。在对116例患者进行基因与图像特征的相关性分析中,从1218个图像特征中选出了8个与HOPX表达相关的显著特征作为放射基因组特征候选,以预测HOPX的表达状态和预后。结果通过叠加集成学习模型建立具有放射基因组特征的影像活检模型,在测试数据集中,模型显示出对HOPX表达的预测能力,ROC曲线下的面积为0.873,Kaplan-Meier曲线的预测能力(P=0.0066)。结论具有放射基因组特征的基于CT图像的活检可以帮助医生预测HOPX在非小细胞肺癌中的表达状况和预后。展开更多
基金Supported by grants from the Zhejiang Medicine and Health Science and Technology Project(No.2018KY748)Ningbo Natural Science Foundation(No.2019A610352)+3 种基金Ningbo Major Scientific and Technological Research and“Unveiling and Commanding”Project(No.2021Z054)Chongqing Science&Technology Commission(No.CSTB2022NSCQ-MSX1413)Ningbo Clinical Research Center for Ophthalmology(No.2022L003)Ningbo Key Laboratory for Neuroretinopathy Medical Research,and the Project of NINGBO Leading Medical&Health Discipline(No.2016-S05).
文摘AIM:To investigate the proliferation regulatory effect of cone-rod homeobox(CRX)in retinal pigment epithelium(RPE)and retinoblastoma(RB)cells to explore the potential application and side effect(oncogenic potential)of CRXbased gene therapy in RPE-based retinopathies.METHODS:Adult human retinal pigment epithelial(ARPE)-19 and human retinal pigment epithelial(RPE)-1 cells and Y79 RB cell were used in the study.Genetic manipulation was performed by lentivirus-based technology.The cell proliferation was determined by a CellTiter-Glo Reagent.The mRNA and protein levels were determined by quantitative real-time polymerase chain reaction(qPCR)and Western blot assay.The transcriptional activity of the promoter was determined by luciferase reporter gene assay.The bindings between CRX and transcription factor 7(TCF7)promoter as well as TCF7 and the promoters of TCF7 target genes were examined by chromatin immunoprecipitation(ChIP)assay.The transcription of the TCF7 was determined by a modified nuclear run-on assay.RESULTS:CRX overexpression and knockdown significantly increased(n=3,P<0.05 in all the cells)and decreased(n=3,P<0.01 in all the cells)the proliferation of RPE and RB cells.CRX overexpression and knockdown significantly increased and deceased the mRNA levels of Wnt signaling target genes[including MYC proto-oncogene(MYC),JUN,FOS like 1(FOSL1),CCND1,cyclin D2(CCND2),cyclin D3(CCND3),cellular communication network factor 4(CCN4),peroxisome proliferator activated receptor delta(PPARD),and matrix metallopeptidase 7(MMP7)]and the luciferase activity driven by the Wnt signaling transcription factor(TCF7).TCF7 overexpression and knockdown significantly increased and decreased the proliferation of RPE and RB cells and depletion of TCF7 significantly abolished the stimulatory effect of CRX on the proliferation of RPE and RB cells.CRX overexpression and knockdown significantly increased and decreased the mRNA level of TCF7 and the promoter of TCF7 was significantly immunoprecipitated by CRX antibody.CONCLUSION:CRX transcriptionally activates TCF7 to promote the proliferation of RPE and RB cells in vitro.CRX is a potential target for RPE-based regenerative medicine.The potential risk of this strategy,tumorigenic potential,should be considered.
文摘Homeobox(HOX)C9,a member of the HOX family,is an important transcription factor,and it plays a significant role in various biological processes.This family of genes is highly valued for their essential roles in establishing and maintaining the body axis during embryonic development and adult tissues.Further,HOXC9 plays a central role in neuronal differentiation,angiogenesis,and adipose distribution,which are essential for the development of the nervous system,maturation of tissues and organs,and maintenance of energy balance and metabolic health.Recent research has found that abnormal HOXC9 expression is closely associated with the development and progression of various tumor types.The HOXC9 expression level can be an indicator of tumor prognosis.Therefore,elucidating the association between HOXC9 expression and its regulatory mechanisms and tumorigenesis can provide novel insights on the diagnosis and treatment of patients with cancer.
基金Supported by the National Natural Science Foundation of China,No.82273457the Natural Science Foundation of Guangdong Province,No.2023A1515012762 and No.2021A1515010846+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis across various organisms,including humans.Comprising six distinct members,from SIX1 to SIX6,each member contributes uniquely to the development and differentiation of diverse tissues and organs,underscoring the versatility of the SIX family.Dysregulation or mutations in SIX genes have been implicated in a spectrum of developmental disorders,as well as in tumor initiation and progression,highlighting their pivotal role in maintaining normal developmental trajectories and cellular functions.Efforts to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor development.While the development of inhibitors targeting this gene family is still in its early stages,the significant potential of such interventions holds promise for future therapeutic advances.Therefore,this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers,focusing on its critical role in normal organ development and its implications in gastrointestinal cancers,including gastric,pancreatic,colorectal cancer,and hepatocellular carcinomas.In conclusion,this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis,prognosis,and treatment of gastrointestinal cancers.
文摘BACKGROUND The distal-less homeobox(DLX)gene family plays an important role in the development of several tumors.However,the expression pattern,prognostic and diagnostic value,possible regulatory mechanisms,and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported.AIM We aimed to comprehensively analyze the biological role of the DLX gene family in the pathogenesis of colon cancer.METHODS Colon cancer tissue and normal colon tissue samples were collected from the Cancer Genome Atlas and Gene Expression Omnibus databases.Wilcoxon rank sum test and t-test were used to assess DLX gene family expression between colon cancer tissue and unpaired normal colon tissue.cBioPortal was used to analyze DLX gene family variants.R software was used to analyze DLX gene expression in colon cancer and the relationship between DLX gene family expression and clinical features and correlation heat map.The survival package and Cox regression module were used to assess the prognostic value of the DLX gene family.The pROC package was used to analyze the diagnostic value of the DLX gene family.R software was used to analyze the possible regulatory mechanisms of DLX gene family members and related genes.The GSVA package was used to analyze the relationship between the DLX gene family and immune infiltration.The ggplot2,the survminer package,and the clusterProfiler package were used for visualization.RESULTS DLX1/2/3/4/5 were significantly aberrantly expressed in colon cancer patients.The expression of DLX genes were associated with M stage,pathologic stage,primary therapy outcome,residual tumor,lymphatic invasion,T stage,N stage,age,perineural invasion,and history of colon polyps.DLX5 was independently correlated with the prognosis of colon cancer in multivariate analysis.DLX1/2/3/4/5/6 were involved in the development and progression of colon cancer by participating in immune infiltration and associated pathways,including the Hippo signaling pathway,the Wnt signaling pathway,several signaling pathways regulating the pluripotency of stem cells,and Staphylococcus aureus infection.CONCLUSION The results of this study suggest a possible role for the DLX gene family as potential diagnostic or prognostic biomarkers and therapeutic targets in colon cancer.
文摘BACKGROUND It is unclear that paired-related homeobox 1(PRRX1)induces epithelialmesenchymal transition(EMT)in oesophageal cancer and the specific function of PRRX1 in oesophageal cancer metastasis.AIM To assess the signicance of PRRX1 expression and investigate the mechanism of EMT in oesophageal cancer metastasis.METHODS Detect the expression of PRRX1 by immunohistochemistry in oesophageal tumour tissues and adjacent normal oesophageal tissues;the PRRX1 short hairpin RNA(shRNA)or blank vector lentiviral gene delivery system was transfected into cells;cell proliferation assay,soft agar colony formation assays,cell invasion and migration assays and animal studies were used to observe cells biological characteristics In vitro and in vivo;XAV939 and LiCl were used to alter the activity of Wnt/β-catenin pathway.Immunofluorescence staining and western blot analysis were used to detect protein expression of EMT markers and Wnt/β-catenin pathway.RESULTS PRRX1 is expressed at high levels in oesophageal cancer specimens and is closely related to tumour metastasis in patients with oesophageal cancer.Regulation of PRRX1 expression might exert obvious effects on cell proliferation,especially the migration and invasion of oesophageal cancer cells.Moreover,silencing PRRX1 expression using a shRNA produced the opposite effects.In addition,when PRRX1 was overexpressed,inhibition of the Wnt/β-catenin pathway with XAV939 negated the effect of PRRX1 on EMT,whereas when PRRX1 was downregulated,activation of the Wnt/β-catenin pathway with LiCl impaired the effect on EMT.CONCLUSION PRRX1 is upregulated in oesophageal cancer is closely correlated with cancer metastasis.Additionally,PRRX1 induces EMT in oesophageal cancer metastasis through activation of Wnt/β-catenin signalling.
文摘目的本研究旨在阐明具有放射基因组特征的基于CT图像的活检以预测非小细胞肺癌(NSCLC)患者仅同源域蛋白同源盒(homeodomain-only protein homeobox,HOPX)基因表达状态和预后。方法根据HOPX的表达将患者标记为HOPX阴性或阳性,并将其分为训练数据集(n=92)和测试数据集(n=24)。在对116例患者进行基因与图像特征的相关性分析中,从1218个图像特征中选出了8个与HOPX表达相关的显著特征作为放射基因组特征候选,以预测HOPX的表达状态和预后。结果通过叠加集成学习模型建立具有放射基因组特征的影像活检模型,在测试数据集中,模型显示出对HOPX表达的预测能力,ROC曲线下的面积为0.873,Kaplan-Meier曲线的预测能力(P=0.0066)。结论具有放射基因组特征的基于CT图像的活检可以帮助医生预测HOPX在非小细胞肺癌中的表达状况和预后。
