In this editorial we provide commentary on the article published by Wang et al,featured in the recent issue of the World Journal of Gastroenterology in 2024.We focus on the metadherin(MTDH),also known as astrocyte ele...In this editorial we provide commentary on the article published by Wang et al,featured in the recent issue of the World Journal of Gastroenterology in 2024.We focus on the metadherin(MTDH),also known as astrocyte elevated gene-1 or lysine rich CEACAM1,and its effects on cancer stem cells(CSCs)and immunity in hepatocellular carcinoma(HCC).HCC is the most common primary liver cancer and one of the leading causes of cancer-related deaths worldwide.Most HCC cases develop in the context of liver cirrhosis.Among the pivotal mechanisms of carcinogenesis are gene mutations,dysregulation of diverse signaling pathways,epigenetic alterations,hepatitis B virus-induced hepatocarcinogenesis,chronic inflammation,impact of tumor microenvironment,oxidative stress.Over the years,extensive research has been conducted on the MTDH role in various tumor pathologies,such as lung,breast,ovarian,gastric,hepatocellular,colorectal,renal carcinoma,neuroblastoma,melanoma,and leukemias.Specifically,its involvement in tumor development processes including transformation,apoptosis evasion,angiogenesis,invasion,and metastasis via multiple signaling pathways.It has been demonstrated that knockdown or knockout of MTDH disrupt tumor development and metastasis.In addition,numerous reports have been carried out regarding the MTDH influence on HCC,demonstrating its role as a predictor of poor prognosis,aggressive tumor phenotypes prone to metastasis and recurrence,and exhibiting significant potential for therapy resistance.Finally,more studies finely investigated the influence of MTDH on CSCs.The CSCs are a small subpopulation of tumor cells that sharing traits with normal stem cells like self-renewal and differentiation abilities,alongside a high plasticity that alters their phenotype.Beyond their presumed role in tumor initiation,they can drive also disease relapse,metastasis,and resistance to chemo and radiotherapy.展开更多
BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of ...BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.展开更多
BACKGROUND The human microRNA 375(MIR375)is significantly downregulated in human colorectal cancer(CRC)and we have previously shown that MIR375 is a CRCassociated miRNA.The metadherin(MTDH)is a candidate target gene o...BACKGROUND The human microRNA 375(MIR375)is significantly downregulated in human colorectal cancer(CRC)and we have previously shown that MIR375 is a CRCassociated miRNA.The metadherin(MTDH)is a candidate target gene of MIR375.AIM To investigate the interaction and function between MIR375 and MTDH in human CRC.METHODS A luciferase reporter system was used to confirm the effect of MIR375 on MTDH expression.The expression levels of MIR375 and the target genes were evaluated by quantitative RT-PCR(qRT-PCR),western blotting,or immunohistochemistry.RESULTS MTDH expression was found to be upregulated in human CRC tissues compared to that in healthy controls.We show that MIR375 regulates the expression of many genes involved in the MTDH-mediated signal transduction pathways[BRAF-MAPK and phosphatidylinositol-4,5-biphosphate-3-kinase catalytic subunit alpha(PIK3CA)-AKT]in CRC cells.Upregulated MTDH expression levels were found to inhibit NF-κB inhibitor alpha,which further upregulated NFKB1 and RELA expression in CRC cells.CONCLUSION Our findings suggest that suppressing MIR375 expression in CRC regulates cell proliferation and angiogenesis by increasing MTDH expression.Thus,MIR375 may be of therapeutic value in treating human CRC.展开更多
Objective:The aim of this study was to detect the expression level of Metadherin (MTDH) in peripheral blood of the breast cancer patients by real-time fluorescence quantitative polymerase chain reaction (PCR),and to e...Objective:The aim of this study was to detect the expression level of Metadherin (MTDH) in peripheral blood of the breast cancer patients by real-time fluorescence quantitative polymerase chain reaction (PCR),and to explore the relationship between expression of Metadherin gene in the patients peripheral blood and the clinic-pathological features in breast cancer. Methods:Real-time fluorescence quantitative polymerase chain reaction was employed to determine the expression level of Metadherin gene in 80 peripheral blood samples of breast cancer patients and healthy donors. Results:The expression of Metadherin gene in breast cancer patients peripheral blood were positive,in which 34 breast cancer patients were highly expressed,accounting for 55.7%,while the expression of Metadherin gene in normal females peripheral blood were negative,there was statistical significance (Ratio = 2.02±0.81,P < 0.05); Ratio of the Metadherin expression in breast cancer patients peripheral blood and the glyceraldehyde-3-phosphate dehydrogenase expression was 1.15 ± 0.36. REST software analysis showed that the expression of Metadherin gene was significantly up-regulated in breast cancer. Conclusion:The SYBR Green I quantitative real-time polymerase chain reaction method can successfully detect the expression level of Metadherin gene. Expression level of Metadherin gene in breast cancer patients peripheral blood is closely related to survival,and it maybe involved in the development of breast cancer and used as an indicator of prognosis.展开更多
[目的]分析异黏蛋白（metadherin,MTDH）在酸性微环境诱导的鼻咽癌紫杉醇耐药中的作用并探讨其相关机制。[方法]不同浓度紫杉醇作用于鼻咽癌细胞CNE-2,48h后CCK-8法检测细胞生长抑制率,确定紫杉醇对CNE-2细胞的IC30。分别用p H 7.4、p H...[目的]分析异黏蛋白（metadherin,MTDH）在酸性微环境诱导的鼻咽癌紫杉醇耐药中的作用并探讨其相关机制。[方法]不同浓度紫杉醇作用于鼻咽癌细胞CNE-2,48h后CCK-8法检测细胞生长抑制率,确定紫杉醇对CNE-2细胞的IC30。分别用p H 7.4、p H 6.8的细胞培养基培养CNE-2细胞,CCK-8法检测IC30浓度紫杉醇下CNE-2细胞生存率;相差显微镜下观察细胞形态改变;RT-q PCR、Western blot检测MTDH及上皮-间质转化（EMT）标志物表达情况;酸性环境下用si RNA沉默MTDH表达后,检测CNE-2细胞对紫杉醇敏感性及EMT标志物表达变化。[结果 ]紫杉醇对CNE-2细胞的IC30为6.167 nmol/L。IC30浓度下,p H6.8组细胞的生存率为48.46%±4.39%,明显高于p H 7.4组的31.30%±5.21%（P=0.013）。酸性环境下沉默MTDH表达后,CNE-2对紫杉醇的敏感性增强,IC30浓度下对照组和沉默组的细胞生存率分别为48.70%±2.35%和32.87%±2.97%（P=0.020）。沉默MTDH表达可逆转酸性引起的E-cadherin下降、Vimentin表达增强。[结论]沉默MTDH可逆转酸性微环境诱导的鼻咽癌CNE-2细胞紫杉醇耐药,这一现象与EMT进程逆转密切相关。展开更多
Protein-metabolite interactions(PMIs)play important roles in various biological processes,especially in disease progression.However,due to the complexity of living cells,it is very difficult to identify specific PMIs....Protein-metabolite interactions(PMIs)play important roles in various biological processes,especially in disease progression.However,due to the complexity of living cells,it is very difficult to identify specific PMIs.Herein,we chose one oncogenic factor,metadherin(MTDH),as a bait to identify its in vivo interacting metabolites in cancer cells.Cholesterol is an important metabolite and essential structural component of cell membranes.It could also drive several diseases including cancer.Interestingly,we found that cholesterol robustly interacted with MTDH and downregulated the expression of MTDH in cancer cells.Furthermore,MTDH disturbed metabolite alterations under cholesterol treatment in MTDH transduced cancer cells.Collectively,our results uncover an undescribed PMI where MTDH,as an oncogenic factor,might positively regulate cancer progression by interacting with choleste rol.This study interprets the theoretical basis of PMI-oriented cancer progression and targeting therapies in clinic.展开更多
目的探讨异黏蛋白(metadherin,MTDH)基因在复发转移乳腺癌患者的表达。方法采用细胞免疫化学方法检测乳腺癌MCF-7、SK-BR3、MDA-MB-231细胞系MTDH基因的表达情况,免疫组化方法检测60例乳腺癌患者术后石蜡组织标本中MTDH基因的表达情况...目的探讨异黏蛋白(metadherin,MTDH)基因在复发转移乳腺癌患者的表达。方法采用细胞免疫化学方法检测乳腺癌MCF-7、SK-BR3、MDA-MB-231细胞系MTDH基因的表达情况,免疫组化方法检测60例乳腺癌患者术后石蜡组织标本中MTDH基因的表达情况。结果 MTDH在乳腺癌细胞株中主要表达于细胞膜及细胞浆中,MTDH基因在复发转移乳腺癌患者中阳性率为73.8%,而原发乳腺癌患者为38.9%(P<0.05)。MTDH基因的表达情况与肿瘤的临床分期(P=0.010)、转移部位(P=0.003)、疾病进展时间(time to progression,TTP)(P=0.002)、Ki67(P=0.029)、P53(P=0.022)以及组织分型(P=0.023)有明显的相关性。但与年龄(P=0.970)、原发淋巴结转移(P=0.694)、HER-2(P=0.282)、ER(P=0.056)、PR(P=0.428)等无明显相关性。结论 MTDH基因有望成为乳腺癌患者重要的独立预后因子。展开更多
文摘In this editorial we provide commentary on the article published by Wang et al,featured in the recent issue of the World Journal of Gastroenterology in 2024.We focus on the metadherin(MTDH),also known as astrocyte elevated gene-1 or lysine rich CEACAM1,and its effects on cancer stem cells(CSCs)and immunity in hepatocellular carcinoma(HCC).HCC is the most common primary liver cancer and one of the leading causes of cancer-related deaths worldwide.Most HCC cases develop in the context of liver cirrhosis.Among the pivotal mechanisms of carcinogenesis are gene mutations,dysregulation of diverse signaling pathways,epigenetic alterations,hepatitis B virus-induced hepatocarcinogenesis,chronic inflammation,impact of tumor microenvironment,oxidative stress.Over the years,extensive research has been conducted on the MTDH role in various tumor pathologies,such as lung,breast,ovarian,gastric,hepatocellular,colorectal,renal carcinoma,neuroblastoma,melanoma,and leukemias.Specifically,its involvement in tumor development processes including transformation,apoptosis evasion,angiogenesis,invasion,and metastasis via multiple signaling pathways.It has been demonstrated that knockdown or knockout of MTDH disrupt tumor development and metastasis.In addition,numerous reports have been carried out regarding the MTDH influence on HCC,demonstrating its role as a predictor of poor prognosis,aggressive tumor phenotypes prone to metastasis and recurrence,and exhibiting significant potential for therapy resistance.Finally,more studies finely investigated the influence of MTDH on CSCs.The CSCs are a small subpopulation of tumor cells that sharing traits with normal stem cells like self-renewal and differentiation abilities,alongside a high plasticity that alters their phenotype.Beyond their presumed role in tumor initiation,they can drive also disease relapse,metastasis,and resistance to chemo and radiotherapy.
基金National Natural Science Foundation of China,No.82173359Basic Research and Frontier Exploration Project of Chongqing and Technology Commission,No.cstc2018jcyjAX0181Kuanren Talents Program of The Second Affiliated Hospital of Chongqing Medical University.
文摘BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.
基金Supported by a grant from the National Research Foundation of Korea,No.2017R1A2B4004801
文摘BACKGROUND The human microRNA 375(MIR375)is significantly downregulated in human colorectal cancer(CRC)and we have previously shown that MIR375 is a CRCassociated miRNA.The metadherin(MTDH)is a candidate target gene of MIR375.AIM To investigate the interaction and function between MIR375 and MTDH in human CRC.METHODS A luciferase reporter system was used to confirm the effect of MIR375 on MTDH expression.The expression levels of MIR375 and the target genes were evaluated by quantitative RT-PCR(qRT-PCR),western blotting,or immunohistochemistry.RESULTS MTDH expression was found to be upregulated in human CRC tissues compared to that in healthy controls.We show that MIR375 regulates the expression of many genes involved in the MTDH-mediated signal transduction pathways[BRAF-MAPK and phosphatidylinositol-4,5-biphosphate-3-kinase catalytic subunit alpha(PIK3CA)-AKT]in CRC cells.Upregulated MTDH expression levels were found to inhibit NF-κB inhibitor alpha,which further upregulated NFKB1 and RELA expression in CRC cells.CONCLUSION Our findings suggest that suppressing MIR375 expression in CRC regulates cell proliferation and angiogenesis by increasing MTDH expression.Thus,MIR375 may be of therapeutic value in treating human CRC.
文摘Objective:The aim of this study was to detect the expression level of Metadherin (MTDH) in peripheral blood of the breast cancer patients by real-time fluorescence quantitative polymerase chain reaction (PCR),and to explore the relationship between expression of Metadherin gene in the patients peripheral blood and the clinic-pathological features in breast cancer. Methods:Real-time fluorescence quantitative polymerase chain reaction was employed to determine the expression level of Metadherin gene in 80 peripheral blood samples of breast cancer patients and healthy donors. Results:The expression of Metadherin gene in breast cancer patients peripheral blood were positive,in which 34 breast cancer patients were highly expressed,accounting for 55.7%,while the expression of Metadherin gene in normal females peripheral blood were negative,there was statistical significance (Ratio = 2.02±0.81,P < 0.05); Ratio of the Metadherin expression in breast cancer patients peripheral blood and the glyceraldehyde-3-phosphate dehydrogenase expression was 1.15 ± 0.36. REST software analysis showed that the expression of Metadherin gene was significantly up-regulated in breast cancer. Conclusion:The SYBR Green I quantitative real-time polymerase chain reaction method can successfully detect the expression level of Metadherin gene. Expression level of Metadherin gene in breast cancer patients peripheral blood is closely related to survival,and it maybe involved in the development of breast cancer and used as an indicator of prognosis.
文摘[目的]分析异黏蛋白（metadherin,MTDH）在酸性微环境诱导的鼻咽癌紫杉醇耐药中的作用并探讨其相关机制。[方法]不同浓度紫杉醇作用于鼻咽癌细胞CNE-2,48h后CCK-8法检测细胞生长抑制率,确定紫杉醇对CNE-2细胞的IC30。分别用p H 7.4、p H 6.8的细胞培养基培养CNE-2细胞,CCK-8法检测IC30浓度紫杉醇下CNE-2细胞生存率;相差显微镜下观察细胞形态改变;RT-q PCR、Western blot检测MTDH及上皮-间质转化（EMT）标志物表达情况;酸性环境下用si RNA沉默MTDH表达后,检测CNE-2细胞对紫杉醇敏感性及EMT标志物表达变化。[结果 ]紫杉醇对CNE-2细胞的IC30为6.167 nmol/L。IC30浓度下,p H6.8组细胞的生存率为48.46%±4.39%,明显高于p H 7.4组的31.30%±5.21%（P=0.013）。酸性环境下沉默MTDH表达后,CNE-2对紫杉醇的敏感性增强,IC30浓度下对照组和沉默组的细胞生存率分别为48.70%±2.35%和32.87%±2.97%（P=0.020）。沉默MTDH表达可逆转酸性引起的E-cadherin下降、Vimentin表达增强。[结论]沉默MTDH可逆转酸性微环境诱导的鼻咽癌CNE-2细胞紫杉醇耐药,这一现象与EMT进程逆转密切相关。
基金the National Natural Science Foundation of China(Nos.81672440,21575142)Innovation Program of Science and Research from the DICP,CAS(No.DICP ZZBS201803)。
文摘Protein-metabolite interactions(PMIs)play important roles in various biological processes,especially in disease progression.However,due to the complexity of living cells,it is very difficult to identify specific PMIs.Herein,we chose one oncogenic factor,metadherin(MTDH),as a bait to identify its in vivo interacting metabolites in cancer cells.Cholesterol is an important metabolite and essential structural component of cell membranes.It could also drive several diseases including cancer.Interestingly,we found that cholesterol robustly interacted with MTDH and downregulated the expression of MTDH in cancer cells.Furthermore,MTDH disturbed metabolite alterations under cholesterol treatment in MTDH transduced cancer cells.Collectively,our results uncover an undescribed PMI where MTDH,as an oncogenic factor,might positively regulate cancer progression by interacting with choleste rol.This study interprets the theoretical basis of PMI-oriented cancer progression and targeting therapies in clinic.
文摘目的探讨异黏蛋白(metadherin,MTDH)基因在复发转移乳腺癌患者的表达。方法采用细胞免疫化学方法检测乳腺癌MCF-7、SK-BR3、MDA-MB-231细胞系MTDH基因的表达情况,免疫组化方法检测60例乳腺癌患者术后石蜡组织标本中MTDH基因的表达情况。结果 MTDH在乳腺癌细胞株中主要表达于细胞膜及细胞浆中,MTDH基因在复发转移乳腺癌患者中阳性率为73.8%,而原发乳腺癌患者为38.9%(P<0.05)。MTDH基因的表达情况与肿瘤的临床分期(P=0.010)、转移部位(P=0.003)、疾病进展时间(time to progression,TTP)(P=0.002)、Ki67(P=0.029)、P53(P=0.022)以及组织分型(P=0.023)有明显的相关性。但与年龄(P=0.970)、原发淋巴结转移(P=0.694)、HER-2(P=0.282)、ER(P=0.056)、PR(P=0.428)等无明显相关性。结论 MTDH基因有望成为乳腺癌患者重要的独立预后因子。
