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
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
Aim： To investigate the stage-specific localization of metastasis-associated protein 1 （MTA1） during spermatogenesis in adult human and mouse testis. Methods： The immunolocalization of MTA1 was studied by immunohi...Aim： To investigate the stage-specific localization of metastasis-associated protein 1 （MTA1） during spermatogenesis in adult human and mouse testis. Methods： The immunolocalization of MTA1 was studied by immunohistochemistry and Western blot analysis. The distribution pattern of MTA1 in mouse testis was confirmed by using quantitative analysis of purified spermatogenic cells. Results： The specificity of polyclonal antibody was confirmed by Western blot analysis. MTA1 was found expressed in the nucleus of germ cells, except elongate spermatids, and in the cytoplasm of Sertoli cells; Leydig cells did not show any specific reactivity. MTA1 possessed different distribution patterns in the two species： in humans, the most intensive staining was found in the nucleus of round spermatids and of primary spermatocytes while in mice, the most intense MTA 1 staining was in the nucleus of leptotene, zygotene and pachytene spermatocytes. In both species the staining exhibited a cyclic pattern. Conclusion： The present communication initially provides new evidence for the potential role of MTA1 in mature testis. In addition, its distinctive expression in germ cells suggests a regulatory role of the peptide during spermatogenesis.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
BACKGROUND Obesity is associated with an increased risk of developing Crohn’s disease(CD),higher disease activity,and comparatively worse clinical outcomes.AIM To investigate the role of mesenteric adipose tissue-der...BACKGROUND Obesity is associated with an increased risk of developing Crohn’s disease(CD),higher disease activity,and comparatively worse clinical outcomes.AIM To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals.METHODS First,we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis.We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1(MALAT1)in mesenteric adipose tissue-derived exosomes and the colon.Next,we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6(ATF6)axis.Finally,we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid(TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways.RESULTS High-fat diet was found to aggravate TNBS-induced colitis in mice.The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased.The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway.This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p.CONCLUSION Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice,which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.展开更多
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.
基金We are grateful to Prof. Rui-An Wang （Department of Molecular and Cellular 0ncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA） for his helpful advice and discussion regarding the pos- sible functions of MTA1. We also thank Miss Hui Wang for her careful assistance in English. This study was supported by the Natural Science Foundation of China （2006： No. 30570982 2003： No. 30370750 2003： No. 30371584）.
文摘Aim： To investigate the stage-specific localization of metastasis-associated protein 1 （MTA1） during spermatogenesis in adult human and mouse testis. Methods： The immunolocalization of MTA1 was studied by immunohistochemistry and Western blot analysis. The distribution pattern of MTA1 in mouse testis was confirmed by using quantitative analysis of purified spermatogenic cells. Results： The specificity of polyclonal antibody was confirmed by Western blot analysis. MTA1 was found expressed in the nucleus of germ cells, except elongate spermatids, and in the cytoplasm of Sertoli cells; Leydig cells did not show any specific reactivity. MTA1 possessed different distribution patterns in the two species： in humans, the most intensive staining was found in the nucleus of round spermatids and of primary spermatocytes while in mice, the most intense MTA 1 staining was in the nucleus of leptotene, zygotene and pachytene spermatocytes. In both species the staining exhibited a cyclic pattern. Conclusion： The present communication initially provides new evidence for the potential role of MTA1 in mature testis. In addition, its distinctive expression in germ cells suggests a regulatory role of the peptide during spermatogenesis.
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 the National Natural Science Foundation of China,No.81770574the Natural Science Foundation of Zhejiang Province,No.LZ21H030002 and No.LY21H030005.
文摘BACKGROUND Obesity is associated with an increased risk of developing Crohn’s disease(CD),higher disease activity,and comparatively worse clinical outcomes.AIM To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals.METHODS First,we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis.We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1(MALAT1)in mesenteric adipose tissue-derived exosomes and the colon.Next,we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6(ATF6)axis.Finally,we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid(TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways.RESULTS High-fat diet was found to aggravate TNBS-induced colitis in mice.The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased.The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway.This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p.CONCLUSION Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice,which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.
基金Supported by the Outstanding Young Scientist Program of the NationalNatural Science Foundation of China ( No 30525036)the ChinaNational Key Program of the International Cooperation for Science and Technology (No 2005DFA30620)
