In this paper,we focus on compelling evidence showing that MEX3A is significantly overexpressed in hepatocellular carcinoma(HCC)and correlates with poor prognosis.A recent study by Ji et al highlights MEX3A’s role in...In this paper,we focus on compelling evidence showing that MEX3A is significantly overexpressed in hepatocellular carcinoma(HCC)and correlates with poor prognosis.A recent study by Ji et al highlights MEX3A’s role in driving proliferation and migration via the RORA/β-catenin axis and epithelial-mesenchymal transition,positioning it as a potential biomarker and therapeutic target.This study addresses a critical gap in understanding HCC pathogenesis and offers valuable mechanistic insights.展开更多
BACKGROUND MEX3A is a member of the human homologous gene MEX-3 family.It has been shown to promote cell proliferation and migration in various cancers,indicating its potential clinical significance.However,the role o...BACKGROUND MEX3A is a member of the human homologous gene MEX-3 family.It has been shown to promote cell proliferation and migration in various cancers,indicating its potential clinical significance.However,the role of MEX3A in hepatocellular carcinoma(HCC)remains largely unexplored,with limited reports available in the literature.AIM To investigate expression and clinical significance of MEX3A in HCC and explore its potential role in tumor progression.METHODS We analyzed MEX3A mRNA expression in HCC and adjacent tissues using data from The Cancer Genome Atlas(TCGA).The correlation between MEX3A expression and overall survival(OS)was evaluated.Immunohistochemistry was performed on HCC surgical specimens to validate MEX3A expression and its association with clinical parameters,including hepatitis B virus(HBV)positivity,tumor differentiation and tumor size.Additionally,MEX3A knockdown HCC cell lines were constructed to explore the biological functions of MEX3A.Cell prolif-eration was assessed using cell counting kit-8 and clone formation assays,while cell cycle progression was analyzed by flow cytometry.The effects of MEX3A on the Wnt/β-catenin signaling pathway were examined by western blotting and immunofluorescence.Cell migration was evaluated using scratch and Transwell assays.Finally,the role of the transcription factor RORA in mediating MEX3A effects was explored by silencing RORA and analyzing its impact on cell proliferation and protein expression.RESULTS TCGA data analysis revealed that MEX3A mRNA expression was significantly higher in HCC tissues compared to adjacent tissues.Higher MEX3A expression was associated with poorer OS.These findings were validated in HCC surgical specimens.Immunohistochemistry confirmed elevated MEX3A expression in HCC tissues and showed positive correlations with Ki-67 and vimentin levels.MEX3A expression was closely related to HBV positivity,tumor differentiation and tumor size.Mechanistic studies demonstrated that MEX3A knockdown inhibited cell proliferation and cell cycle progression,as shown by reduced expression ofβ-catenin,c-Myc and cyclin D1.Additionally,MEX3A knockdown inhibited the nuclear entry ofβ-catenin,thereby suppressing the activation of downstream oncogenic pathways.MEX3A depletion significantly reduced the migratory ability of HCC cells,likely through downregulation of the epithelial-mesenchymal transition pathway.Transcription factor analysis identified RORA as a potential mediator of MEX3A effects.Silencing RORA antagonized the effects of MEX3A on cell proliferation and the expression ofβ-catenin,c-Myc and cyclin D1.CONCLUSION MEX3A promotes cell proliferation in HCC by regulating the RORA/β-catenin pathway.Our findings suggest that MEX3A could serve as a prognostic marker and therapeutic target for HCC.展开更多
This article discusses the recently published study by Ji et al on the role of MEX3A in hepatocellular carcinoma.The study reveals MEX3A’s role,but has issues including a small sample size and unclear RORA-regulation...This article discusses the recently published study by Ji et al on the role of MEX3A in hepatocellular carcinoma.The study reveals MEX3A’s role,but has issues including a small sample size and unclear RORA-regulation.We propose new research directions.It is essential to analyze the immune cells in MEX3A-high tumors and test the impact of MEX3A-knockout on immunotherapy when exploring the relationship between MEX3A and the immune microenvironment.With regard to MEX3A and cancer stem cells,it is necessary to assess the effect of MEX3A on cancer stem cell self-renewal and use organoids to test the targeting ability of MEX3A-inhibitors.In addition,improvements such as larger-scale validation and in-depth mechanism research are required,which could boost hepatocellular carcinoma understanding and patient prognosis.展开更多
目的探讨Mex3C-1对卡巴胆碱诱导的Fos表达的影响。方法将具有可持续表达人Mex3C-1序列的质粒pLV-CMV-Mex3C(OE)在HEK293T细胞中包装成慢病毒载体,同时制备非特异性对照(NC)CmiR0001-MR03的慢病毒载体,分别感染人神经母细胞瘤细胞SH-SY5Y...目的探讨Mex3C-1对卡巴胆碱诱导的Fos表达的影响。方法将具有可持续表达人Mex3C-1序列的质粒pLV-CMV-Mex3C(OE)在HEK293T细胞中包装成慢病毒载体,同时制备非特异性对照(NC)CmiR0001-MR03的慢病毒载体,分别感染人神经母细胞瘤细胞SH-SY5Y,经嘌呤霉素筛选后得到稳定高表达Mex3C-1和阴性对照细胞系,用Real time PCR和Western blot方法检测Mex3C-1的基因和蛋白表达效果。之后用卡巴胆碱诱导Fos表达,在诱导0、30、60、90和120min后分别提取mRNA,采用Real time PCR方法检测Fos mRNA的相对表达量。结果Real time PCR检测结果显示,OE组的Mex3C-1 mRNA的相对表达量(21.11±0.60)高于NC组(1.03±0.13)(t=32.63,P=0.000)。Western blot结果显示,在82kDa处OE组的Mex3C-1蛋白表达量高于NC组(P<0.001)。Real time PCR检测不同干预时间两组Fos mRNA,除0min外各个时间点OE组均高于NC组,表明Mex3C-1的过表达可以明显上调Fos mRNA的表达;NC组于120min时已基本恢复至基础值,而OE组120min时Fos mRNA表达量仍然较高,Mex3C-1过表达可以延长Fos mRNA的半衰期,增强其稳定性,OE组与阴性对照NC组比较,Fos mRNA表达量差异有统计学意义(F=287.069,P=0.000)。结论持续过表达Mex3C-1的人神经母细胞瘤SH-SY5Y细胞系建立成功,且Mex3C-1过表达能够明显增强卡巴胆碱诱导的Fos表达程度并增强其稳定性。展开更多
基金Supported by Youth Foundation of Henan Scientific Committee,No.202300410416Henan Province Medical Science,Technology Breakthrough Plan Project,No.LHGJ20190033.
文摘In this paper,we focus on compelling evidence showing that MEX3A is significantly overexpressed in hepatocellular carcinoma(HCC)and correlates with poor prognosis.A recent study by Ji et al highlights MEX3A’s role in driving proliferation and migration via the RORA/β-catenin axis and epithelial-mesenchymal transition,positioning it as a potential biomarker and therapeutic target.This study addresses a critical gap in understanding HCC pathogenesis and offers valuable mechanistic insights.
基金Supported by Suzhou Municipal Science and Technology Bureau,No.SYS2020081.
文摘BACKGROUND MEX3A is a member of the human homologous gene MEX-3 family.It has been shown to promote cell proliferation and migration in various cancers,indicating its potential clinical significance.However,the role of MEX3A in hepatocellular carcinoma(HCC)remains largely unexplored,with limited reports available in the literature.AIM To investigate expression and clinical significance of MEX3A in HCC and explore its potential role in tumor progression.METHODS We analyzed MEX3A mRNA expression in HCC and adjacent tissues using data from The Cancer Genome Atlas(TCGA).The correlation between MEX3A expression and overall survival(OS)was evaluated.Immunohistochemistry was performed on HCC surgical specimens to validate MEX3A expression and its association with clinical parameters,including hepatitis B virus(HBV)positivity,tumor differentiation and tumor size.Additionally,MEX3A knockdown HCC cell lines were constructed to explore the biological functions of MEX3A.Cell prolif-eration was assessed using cell counting kit-8 and clone formation assays,while cell cycle progression was analyzed by flow cytometry.The effects of MEX3A on the Wnt/β-catenin signaling pathway were examined by western blotting and immunofluorescence.Cell migration was evaluated using scratch and Transwell assays.Finally,the role of the transcription factor RORA in mediating MEX3A effects was explored by silencing RORA and analyzing its impact on cell proliferation and protein expression.RESULTS TCGA data analysis revealed that MEX3A mRNA expression was significantly higher in HCC tissues compared to adjacent tissues.Higher MEX3A expression was associated with poorer OS.These findings were validated in HCC surgical specimens.Immunohistochemistry confirmed elevated MEX3A expression in HCC tissues and showed positive correlations with Ki-67 and vimentin levels.MEX3A expression was closely related to HBV positivity,tumor differentiation and tumor size.Mechanistic studies demonstrated that MEX3A knockdown inhibited cell proliferation and cell cycle progression,as shown by reduced expression ofβ-catenin,c-Myc and cyclin D1.Additionally,MEX3A knockdown inhibited the nuclear entry ofβ-catenin,thereby suppressing the activation of downstream oncogenic pathways.MEX3A depletion significantly reduced the migratory ability of HCC cells,likely through downregulation of the epithelial-mesenchymal transition pathway.Transcription factor analysis identified RORA as a potential mediator of MEX3A effects.Silencing RORA antagonized the effects of MEX3A on cell proliferation and the expression ofβ-catenin,c-Myc and cyclin D1.CONCLUSION MEX3A promotes cell proliferation in HCC by regulating the RORA/β-catenin pathway.Our findings suggest that MEX3A could serve as a prognostic marker and therapeutic target for HCC.
文摘This article discusses the recently published study by Ji et al on the role of MEX3A in hepatocellular carcinoma.The study reveals MEX3A’s role,but has issues including a small sample size and unclear RORA-regulation.We propose new research directions.It is essential to analyze the immune cells in MEX3A-high tumors and test the impact of MEX3A-knockout on immunotherapy when exploring the relationship between MEX3A and the immune microenvironment.With regard to MEX3A and cancer stem cells,it is necessary to assess the effect of MEX3A on cancer stem cell self-renewal and use organoids to test the targeting ability of MEX3A-inhibitors.In addition,improvements such as larger-scale validation and in-depth mechanism research are required,which could boost hepatocellular carcinoma understanding and patient prognosis.
文摘目的探讨Mex3C-1对卡巴胆碱诱导的Fos表达的影响。方法将具有可持续表达人Mex3C-1序列的质粒pLV-CMV-Mex3C(OE)在HEK293T细胞中包装成慢病毒载体,同时制备非特异性对照(NC)CmiR0001-MR03的慢病毒载体,分别感染人神经母细胞瘤细胞SH-SY5Y,经嘌呤霉素筛选后得到稳定高表达Mex3C-1和阴性对照细胞系,用Real time PCR和Western blot方法检测Mex3C-1的基因和蛋白表达效果。之后用卡巴胆碱诱导Fos表达,在诱导0、30、60、90和120min后分别提取mRNA,采用Real time PCR方法检测Fos mRNA的相对表达量。结果Real time PCR检测结果显示,OE组的Mex3C-1 mRNA的相对表达量(21.11±0.60)高于NC组(1.03±0.13)(t=32.63,P=0.000)。Western blot结果显示,在82kDa处OE组的Mex3C-1蛋白表达量高于NC组(P<0.001)。Real time PCR检测不同干预时间两组Fos mRNA,除0min外各个时间点OE组均高于NC组,表明Mex3C-1的过表达可以明显上调Fos mRNA的表达;NC组于120min时已基本恢复至基础值,而OE组120min时Fos mRNA表达量仍然较高,Mex3C-1过表达可以延长Fos mRNA的半衰期,增强其稳定性,OE组与阴性对照NC组比较,Fos mRNA表达量差异有统计学意义(F=287.069,P=0.000)。结论持续过表达Mex3C-1的人神经母细胞瘤SH-SY5Y细胞系建立成功,且Mex3C-1过表达能够明显增强卡巴胆碱诱导的Fos表达程度并增强其稳定性。
