BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of canc...BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer cells.Long non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and growth.AIM To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 cells.METHODS CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration.Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation.Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway.Additionally,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.RESULTS hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1.hBD-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I protein.Furthermore,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR pathway.The lncRNA TCONS_00014506 was ultimately selected.Following the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein expression.CONCLUSION hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.展开更多
BACKGROUND Clinical prognosis often worsens due to high recurrence rates following radical surgery for colon cancer.The examination of high-risk recurrence factors post-surgery provides critical insights for disease e...BACKGROUND Clinical prognosis often worsens due to high recurrence rates following radical surgery for colon cancer.The examination of high-risk recurrence factors post-surgery provides critical insights for disease evaluation and treatment planning.AIM To explore the relationship between metastasis-associated factor-1 in colon cancer(MACC1)and vacuolar ATP synthase(V-ATPase)expression in colon cancer tissues,and recurrence rate in patients undergoing radical colon cancer surgery.METHODS We selected 104 patients treated with radical colon cancer surgery at our hospital from January 2018 to June 2021.Immunohistochemical staining was utilized to assess the expression levels of MACC1 and V-ATPase in these patients.RESULTS The rates of MACC1 and V-ATPase positivity were 64.42%and 67.31%,respe-ctively,in colon cancer tissues,which were significantly higher than in paracan-cerous tissues(P<0.05).Among patients with TNM stage III,medium to low differentiation,and lymph node metastasis,the positive rates of MACC1 and V-ATPase were significantly elevated in comparison to patients with TNM stage I-II,high differentiation,and no lymph node metastasis(P<0.05).The rate of MACC1 positivity was 76.67%in patients with tumor diameters>5 cm,notably higher than in patients with tumor diameters≤5 cm(P<0.05).We observed a positive correlation between MACC1 and V-ATPase expression(rs=0.797,P<0.05).The positive rates of MACC1 and V-ATPase were significantly higher in patients with recurrence compared to those without(P<0.05).Logistic regression analysis revealed TNM stage,lymph node metastasis,MACC1 expression,and V-ATPase expression as risk factors for postoperative colon cancer recurrence(OR=6.322,3.435,2.683,and 2.421;P<0.05).CONCLUSION The upregulated expression of MACC1 and V-ATPase in colon cancer patients appears to correlate with clinicopathological features and post-radical surgery recurrence.展开更多
The role of lncRNA KCNQ1 opposite strand/antisense transcript 1(KCNQ1OT1)in colon cancer involves various tumorigenic processes and has been studed widely.However,the mechanism by which it promotes colon cancer remain...The role of lncRNA KCNQ1 opposite strand/antisense transcript 1(KCNQ1OT1)in colon cancer involves various tumorigenic processes and has been studed widely.However,the mechanism by which it promotes colon cancer remains unclear.Retrovirnl vector pSEB61 was retroftted in established HCT116 siKCN and SW480-siKCN cells to silence KCNQ1 OT1.Cellular proliferation was measured using CCK8 assay,and flow cytometry(FCM)detected cell cydle changes.RNA sequencing(RNA Seq)analysis showed differentially expressed genes(DEGs).Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were carried out to analyze enriched functions and signaling pathways.RT-qPCR,immunofluorescence,and western blotting were carried out to validate downstream gene expressions.The effects of tumorigenesis were evaluated in BALB/c nude mice by tumor xenografts.Our data revealed that the silencing of KONQ1OT1 in HCT116 and SW480 cells slowed cell growth and decreased the number of cells in the G2/M phase.RNA-Seq analysis showed the data of DEGs enriched in various GO and KEGG pathways such as DNA replication and cell cyde.RT qPCR,immunofluorescence,and western blotting confirmed downstream CCNE2 and PCNA gene expressions.HCT116 siKCN cells signifcantly suppressed tumorigenesis in BALB/c nude mice.Our study suggests that lncRNA KCNQ1OT1 may provide a promising therapeutic strategy for colon cancer.展开更多
BACKGROUND Heterogeneous ribonucleoprotein A1(hnRNPA1)has been reported to enhance the Warburg effect and promote colon cancer(CC)cell proliferation,but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in ...BACKGROUND Heterogeneous ribonucleoprotein A1(hnRNPA1)has been reported to enhance the Warburg effect and promote colon cancer(CC)cell proliferation,but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated.AIM To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway.METHODS Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b.The relationship between the expression values and the clinicopathological features of the patients was investigated.Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction,while differences in protein expression were analyzed using western blot.Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2’-deoxyuridine assays,and cell cycle and apoptosis were detected using flow cytometric assays.The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay.The Warburg effect was evaluated by glucose uptake and lactic acid production assays.RESULTS The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls(P<0.05).Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC,including stage I,II-III,and IV.Furthermore,the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification.HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway,thereby promoting proliferation of HCT116 and SW620 cells.However,the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b,effectively blocking the Warburg effect.CONCLUSION These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.展开更多
Objective： The aim of this study was to detect metastasis-associated in colon cancer-1 （MACC1） expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival. ...Objective： The aim of this study was to detect metastasis-associated in colon cancer-1 （MACC1） expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival. Methods： The expression of MACC1 and c-MET protein in a sample of 128 gastric cancer tissues was detected by immunohistochemistry. A retrospective cohort study on the prognosis was carried out and data were collected from medical records. Results： The positive rate of MACC1 protein expression in gastric cancer was 47.66%, higher than that in adjacent noncancerous mucosa （P0.001）. MACC1 protein expression was not related to the clinicopathological variables involved. Kaplan-Meier analysis revealed that the survival of MACC1 positive group tended to be better than that of MACC1 negative group, particularly in patients with stage III carcinoma （P=0.032）. Cox regression analysis revealed that MACC1 protein over-expression in gastric cancer tended to be a protective factor with hazard ratio of 0.621 （P=0.057）. Immunohistochemical analysis showed that the positive rate of c-MET protein expression was much higher in cases with positive MACC1 expression in gastric cancer （P=0.002）, but P53 expression was not associated with MACC1 expression. Conclusion： MACC1 over-expression implies better survival and may be an independent prognostic factor for gastric cancer in Chinese patients.展开更多
Metastasis-associated in colon cancer-1(MACC1) is an oncogene that was first identified in colon cancer. The upstream and downstream of MACC1 form a delicate regulatory network that supports its tumorigenic role in ca...Metastasis-associated in colon cancer-1(MACC1) is an oncogene that was first identified in colon cancer. The upstream and downstream of MACC1 form a delicate regulatory network that supports its tumorigenic role in cancers. Multiple functions of MACC1 have been discovered in many cancers. In gastric cancer(GC), MACC1 has been shown to be involved in oncogenesis and t umor progression. MACC1 overexpression adversely affects the clinical outcomes of GC patients. Regarding the mechanism of action of MACC1 in GC, studies have shown that it promotes the epithelialto-mesenchymal transition and accelerates cancer metastasis. MACC1 is involved in many hallmarks of GC in addition to metastasis. MACC1 promotes vasculogenic mimicry(VM) via TWIST1/2, and VM increases the tumor blood supply, which is necessary for tumor progression. MACC1 also facilitates GC lymphangiogenesis by upregulating extracellular secretion of VEGF-C/D, indicating that MACC1 may be an important player in GC lymphatic dissemination. Additionally, MACC1 supports GC growth under metabolic stress by enhancing the Warburg effect. In conclusion, MACC1 participates in multiple biological processes inside and outside of GC cells, making it an important mediator of the tumor microenvironment.展开更多
AIM: To investigate the intratumoral expression of metastasis-associated in colon cancer 1 (MACC1) and c-Met and determine their clinical values associated with hepatitis B virus (HBV)-related hepatocellular carcinoma...AIM: To investigate the intratumoral expression of metastasis-associated in colon cancer 1 (MACC1) and c-Met and determine their clinical values associated with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: A retrospective study admitted three hundred fifty-four patients with HBV-related HCC. The expression and distribution of MACC1 and c-Met were assessed by quantitative real-time polymerase chain reaction and immunohistochemistry staining. Prognostic factors influencing survival, metastasis and recurrence were assessed. RESULTS: Intratumoral MACC1 level was found to be associated with HCC disease progression. Both median tumor-free survival (TFS) and overall survival (OS) were significantly shorter in the postoperative HCC patients with high intratumoral MACC1 expression, as compared to those with low intratumoral MACC1 levels (TFS: 34 mo vs 48.0 mo, P < 0.001; OS: 40 mo vs 48 mo, P < 0.01). Multivariable analysis indicated that high MACC1 expression or co-expression with c-Met were independent predictors for HCC clinic outcome (P < 0.001). CONCLUSION: High intratumoral MACC1 expression can be associated with enhanced tumor progression and poor outcome of HBV-related HCC. MACC1 may serve as a prognostic biomarker for postoperative HCC.展开更多
[Objectives] To investigate the role of Eriocalyxin B (EriB) in promoting colon cancer cell apoptosis through ERK1/2 pathway in vitro, and to provide a natural candidate drug for colon cancer treatment. [Methods] Colo...[Objectives] To investigate the role of Eriocalyxin B (EriB) in promoting colon cancer cell apoptosis through ERK1/2 pathway in vitro, and to provide a natural candidate drug for colon cancer treatment. [Methods] Colon cancer cells treated with different concentrations of EriB were detected by CCK-8 assay;cell scratch assay and crystal violet staining were used to detect the invasion and migration of colon cancer cell;cell apoptosis was detected by Annexin V/PI double staining, and cell cycle was detected by PI staining;Western Blotting was used to detect epithelial-mesenchymal transition and apoptosis-related proteins in colon cancer cells treated with EriB. [Results] After EriB treatment, the proliferation, migration and apoptosis of colon cancer cells were significantly inhibited, and the ratio of P-ERK1/2 to ERK was significantly decreased. [Conclusions] EriB can effectively inhibit the proliferation of colon cancer cells and promote the apoptosis of colon cancer cells through ERK1/2 pathway.展开更多
AIM:To study the correlation between high metastasisassociated protein 1(MTA1)expression and lymphangiogenesis in colorectal cancer(CRC)and its role in production of vascular endothelial growth factor-C(VEGF-C). METHO...AIM:To study the correlation between high metastasisassociated protein 1(MTA1)expression and lymphangiogenesis in colorectal cancer(CRC)and its role in production of vascular endothelial growth factor-C(VEGF-C). METHODS:Impact of high MTA1 and VEGF-C expression levels on disease progression and lymphovasculardensity(LVD,D2-40-immunolabeled)in 81 cases of human CRC was evaluated by immunohistochemistry. VEGF-C mRNA and protein expressions in human LoVo and HCT116 cell lines were detected by real-time polymerase chain reaction and Western blotting,respectively,with a stable expression vector or siRNA. RESULTS:The elevated MTA1 and VEGF-C expression levels were correlated with lymph node metastasis and Dukes stages(P<0.05).Additionally,high MTA1 expression level was correlated with a large tumor size(P< 0.05).A significant correlation was found between MTA1 and VEGF-C protein expressions in tumor cells(r=0.371, P<0.05).Similar to the VEGF-C expression level,high MTA1 expression level was correlated with high LVD in CRC(P<0.05).Furthermore,over-expression of MTA1 significantly enhanced the VEGF-C mRNA and protein expression levels,whereas siRNAs-knocked down MTA1 decreased the VEGF-C expression level. CONCLUSION:MTA1,as a regulator of tumor-associated lymphangiogenesis,promotes lymphangiogenesis in CRC by mediating the VEGF-C expression.展开更多
恶性肿瘤的发生严重威胁着人类的健康及生存,对于其发病机制及转移机制仍然不是十分清楚。结肠癌转移关联基因1 (Metastasis-Associated in Colon Cancer 1,MACC1)是2009年发现的与结肠癌的发生密切相关的基因,不仅诱导肿瘤的发生、转移...恶性肿瘤的发生严重威胁着人类的健康及生存,对于其发病机制及转移机制仍然不是十分清楚。结肠癌转移关联基因1 (Metastasis-Associated in Colon Cancer 1,MACC1)是2009年发现的与结肠癌的发生密切相关的基因,不仅诱导肿瘤的发生、转移,且与肿瘤患者的预后及生存率明显相关,这主要与MACC1调节HGF/c-Met信号通路有关。在未来,MACC1有望成为肿瘤基因治疗的新靶点。本篇结合国内外的文献,就MACC1在肿瘤发生发展及转移过程的研究进展作一综述。展开更多
基金Supported by National Natural Science Foundation of China,No.82360329Inner Mongolia Medical University General Project,No.YKD2023MS047Inner Mongolia Health Commission Science and Technology Plan Project,No.202201275.
文摘BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer cells.Long non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and growth.AIM To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 cells.METHODS CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration.Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation.Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway.Additionally,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.RESULTS hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1.hBD-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I protein.Furthermore,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR pathway.The lncRNA TCONS_00014506 was ultimately selected.Following the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein expression.CONCLUSION hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.
基金The study was reviewed and approved by the Institutional Review Board of The First Affiliated Hospital of Gannan Medical College,No.20141219.
文摘BACKGROUND Clinical prognosis often worsens due to high recurrence rates following radical surgery for colon cancer.The examination of high-risk recurrence factors post-surgery provides critical insights for disease evaluation and treatment planning.AIM To explore the relationship between metastasis-associated factor-1 in colon cancer(MACC1)and vacuolar ATP synthase(V-ATPase)expression in colon cancer tissues,and recurrence rate in patients undergoing radical colon cancer surgery.METHODS We selected 104 patients treated with radical colon cancer surgery at our hospital from January 2018 to June 2021.Immunohistochemical staining was utilized to assess the expression levels of MACC1 and V-ATPase in these patients.RESULTS The rates of MACC1 and V-ATPase positivity were 64.42%and 67.31%,respe-ctively,in colon cancer tissues,which were significantly higher than in paracan-cerous tissues(P<0.05).Among patients with TNM stage III,medium to low differentiation,and lymph node metastasis,the positive rates of MACC1 and V-ATPase were significantly elevated in comparison to patients with TNM stage I-II,high differentiation,and no lymph node metastasis(P<0.05).The rate of MACC1 positivity was 76.67%in patients with tumor diameters>5 cm,notably higher than in patients with tumor diameters≤5 cm(P<0.05).We observed a positive correlation between MACC1 and V-ATPase expression(rs=0.797,P<0.05).The positive rates of MACC1 and V-ATPase were significantly higher in patients with recurrence compared to those without(P<0.05).Logistic regression analysis revealed TNM stage,lymph node metastasis,MACC1 expression,and V-ATPase expression as risk factors for postoperative colon cancer recurrence(OR=6.322,3.435,2.683,and 2.421;P<0.05).CONCLUSION The upregulated expression of MACC1 and V-ATPase in colon cancer patients appears to correlate with clinicopathological features and post-radical surgery recurrence.
基金the Scientific Research Project of Anhui Provincial Health Commission in 2021(#AHWJ2021b109 to LS)Scientific and Technological Research Program of Chongqing Municipal Education Commission(#KJZD-K201900402 to TZ)+1 种基金Special Fund for Wannan Medical College Scholar Project(#WK2021F07)Educational Commission of Anhui Province of China(2022AH051241).
文摘The role of lncRNA KCNQ1 opposite strand/antisense transcript 1(KCNQ1OT1)in colon cancer involves various tumorigenic processes and has been studed widely.However,the mechanism by which it promotes colon cancer remains unclear.Retrovirnl vector pSEB61 was retroftted in established HCT116 siKCN and SW480-siKCN cells to silence KCNQ1 OT1.Cellular proliferation was measured using CCK8 assay,and flow cytometry(FCM)detected cell cydle changes.RNA sequencing(RNA Seq)analysis showed differentially expressed genes(DEGs).Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were carried out to analyze enriched functions and signaling pathways.RT-qPCR,immunofluorescence,and western blotting were carried out to validate downstream gene expressions.The effects of tumorigenesis were evaluated in BALB/c nude mice by tumor xenografts.Our data revealed that the silencing of KONQ1OT1 in HCT116 and SW480 cells slowed cell growth and decreased the number of cells in the G2/M phase.RNA-Seq analysis showed the data of DEGs enriched in various GO and KEGG pathways such as DNA replication and cell cyde.RT qPCR,immunofluorescence,and western blotting confirmed downstream CCNE2 and PCNA gene expressions.HCT116 siKCN cells signifcantly suppressed tumorigenesis in BALB/c nude mice.Our study suggests that lncRNA KCNQ1OT1 may provide a promising therapeutic strategy for colon cancer.
基金Supported by the National Natural Science Foundation of China,No.82160405Jiangxi Provincial Natural Science Foundation,No.20232BAB206131,No.20212ACB206016,and No.20224BAB206114+1 种基金Jiangxi Provincial Health Commission Project,No.202310887the Development Fund of Jiangxi Cancer Hospital,No.2021J10.
文摘BACKGROUND Heterogeneous ribonucleoprotein A1(hnRNPA1)has been reported to enhance the Warburg effect and promote colon cancer(CC)cell proliferation,but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated.AIM To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway.METHODS Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b.The relationship between the expression values and the clinicopathological features of the patients was investigated.Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction,while differences in protein expression were analyzed using western blot.Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2’-deoxyuridine assays,and cell cycle and apoptosis were detected using flow cytometric assays.The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay.The Warburg effect was evaluated by glucose uptake and lactic acid production assays.RESULTS The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls(P<0.05).Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC,including stage I,II-III,and IV.Furthermore,the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification.HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway,thereby promoting proliferation of HCT116 and SW620 cells.However,the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b,effectively blocking the Warburg effect.CONCLUSION These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.
基金supported by the grants of the Foundation from Beijing Municipal Committee of Science and Technology (No. D0905001040631)the Scientific Research Foundation for the Returned Overseas Chinese Scholars from Ministry of Education of China
文摘Objective： The aim of this study was to detect metastasis-associated in colon cancer-1 （MACC1） expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival. Methods： The expression of MACC1 and c-MET protein in a sample of 128 gastric cancer tissues was detected by immunohistochemistry. A retrospective cohort study on the prognosis was carried out and data were collected from medical records. Results： The positive rate of MACC1 protein expression in gastric cancer was 47.66%, higher than that in adjacent noncancerous mucosa （P0.001）. MACC1 protein expression was not related to the clinicopathological variables involved. Kaplan-Meier analysis revealed that the survival of MACC1 positive group tended to be better than that of MACC1 negative group, particularly in patients with stage III carcinoma （P=0.032）. Cox regression analysis revealed that MACC1 protein over-expression in gastric cancer tended to be a protective factor with hazard ratio of 0.621 （P=0.057）. Immunohistochemical analysis showed that the positive rate of c-MET protein expression was much higher in cases with positive MACC1 expression in gastric cancer （P=0.002）, but P53 expression was not associated with MACC1 expression. Conclusion： MACC1 over-expression implies better survival and may be an independent prognostic factor for gastric cancer in Chinese patients.
文摘Metastasis-associated in colon cancer-1(MACC1) is an oncogene that was first identified in colon cancer. The upstream and downstream of MACC1 form a delicate regulatory network that supports its tumorigenic role in cancers. Multiple functions of MACC1 have been discovered in many cancers. In gastric cancer(GC), MACC1 has been shown to be involved in oncogenesis and t umor progression. MACC1 overexpression adversely affects the clinical outcomes of GC patients. Regarding the mechanism of action of MACC1 in GC, studies have shown that it promotes the epithelialto-mesenchymal transition and accelerates cancer metastasis. MACC1 is involved in many hallmarks of GC in addition to metastasis. MACC1 promotes vasculogenic mimicry(VM) via TWIST1/2, and VM increases the tumor blood supply, which is necessary for tumor progression. MACC1 also facilitates GC lymphangiogenesis by upregulating extracellular secretion of VEGF-C/D, indicating that MACC1 may be an important player in GC lymphatic dissemination. Additionally, MACC1 supports GC growth under metabolic stress by enhancing the Warburg effect. In conclusion, MACC1 participates in multiple biological processes inside and outside of GC cells, making it an important mediator of the tumor microenvironment.
基金Supported by Grants from the Key Scientific and Technological Research Foundation of the National Special-purpose Program,No. 2008ZX10002-018from the Capital Medical Development and Research in Beijing, China, No. 2007-1021 and2009-2041
文摘AIM: To investigate the intratumoral expression of metastasis-associated in colon cancer 1 (MACC1) and c-Met and determine their clinical values associated with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: A retrospective study admitted three hundred fifty-four patients with HBV-related HCC. The expression and distribution of MACC1 and c-Met were assessed by quantitative real-time polymerase chain reaction and immunohistochemistry staining. Prognostic factors influencing survival, metastasis and recurrence were assessed. RESULTS: Intratumoral MACC1 level was found to be associated with HCC disease progression. Both median tumor-free survival (TFS) and overall survival (OS) were significantly shorter in the postoperative HCC patients with high intratumoral MACC1 expression, as compared to those with low intratumoral MACC1 levels (TFS: 34 mo vs 48.0 mo, P < 0.001; OS: 40 mo vs 48 mo, P < 0.01). Multivariable analysis indicated that high MACC1 expression or co-expression with c-Met were independent predictors for HCC clinic outcome (P < 0.001). CONCLUSION: High intratumoral MACC1 expression can be associated with enhanced tumor progression and poor outcome of HBV-related HCC. MACC1 may serve as a prognostic biomarker for postoperative HCC.
基金Supported by Natural Science Research Project of Colleges and Universities in Anhui Province(KJ2019A1110,KJ2020A0863)Innovation Team Research Fund Project of Anhui Medical College(WJH202007t,WJH202008t)2021 Anhui Provincial Production-Education Integration Training Base Project for Quality Engineering(2021cjrh020).
文摘[Objectives] To investigate the role of Eriocalyxin B (EriB) in promoting colon cancer cell apoptosis through ERK1/2 pathway in vitro, and to provide a natural candidate drug for colon cancer treatment. [Methods] Colon cancer cells treated with different concentrations of EriB were detected by CCK-8 assay;cell scratch assay and crystal violet staining were used to detect the invasion and migration of colon cancer cell;cell apoptosis was detected by Annexin V/PI double staining, and cell cycle was detected by PI staining;Western Blotting was used to detect epithelial-mesenchymal transition and apoptosis-related proteins in colon cancer cells treated with EriB. [Results] After EriB treatment, the proliferation, migration and apoptosis of colon cancer cells were significantly inhibited, and the ratio of P-ERK1/2 to ERK was significantly decreased. [Conclusions] EriB can effectively inhibit the proliferation of colon cancer cells and promote the apoptosis of colon cancer cells through ERK1/2 pathway.
基金Supported by National Natural Science Foundation of China(No.30772131)Fundamental Research Funds for Central Universities(No.21609313)from Ministry of Education of China
文摘AIM:To study the correlation between high metastasisassociated protein 1(MTA1)expression and lymphangiogenesis in colorectal cancer(CRC)and its role in production of vascular endothelial growth factor-C(VEGF-C). METHODS:Impact of high MTA1 and VEGF-C expression levels on disease progression and lymphovasculardensity(LVD,D2-40-immunolabeled)in 81 cases of human CRC was evaluated by immunohistochemistry. VEGF-C mRNA and protein expressions in human LoVo and HCT116 cell lines were detected by real-time polymerase chain reaction and Western blotting,respectively,with a stable expression vector or siRNA. RESULTS:The elevated MTA1 and VEGF-C expression levels were correlated with lymph node metastasis and Dukes stages(P<0.05).Additionally,high MTA1 expression level was correlated with a large tumor size(P< 0.05).A significant correlation was found between MTA1 and VEGF-C protein expressions in tumor cells(r=0.371, P<0.05).Similar to the VEGF-C expression level,high MTA1 expression level was correlated with high LVD in CRC(P<0.05).Furthermore,over-expression of MTA1 significantly enhanced the VEGF-C mRNA and protein expression levels,whereas siRNAs-knocked down MTA1 decreased the VEGF-C expression level. CONCLUSION:MTA1,as a regulator of tumor-associated lymphangiogenesis,promotes lymphangiogenesis in CRC by mediating the VEGF-C expression.
文摘恶性肿瘤的发生严重威胁着人类的健康及生存,对于其发病机制及转移机制仍然不是十分清楚。结肠癌转移关联基因1 (Metastasis-Associated in Colon Cancer 1,MACC1)是2009年发现的与结肠癌的发生密切相关的基因,不仅诱导肿瘤的发生、转移,且与肿瘤患者的预后及生存率明显相关,这主要与MACC1调节HGF/c-Met信号通路有关。在未来,MACC1有望成为肿瘤基因治疗的新靶点。本篇结合国内外的文献,就MACC1在肿瘤发生发展及转移过程的研究进展作一综述。
