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
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 M展开更多
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
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
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.
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 M
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.
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。
