BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact mo...BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.展开更多
BACKGROUND Colorectal cancer(CRC)is a common malignant tumor of the digestive tract worldwide,characterized by high incidence and mortality rates.AIM To investigate the expression of serum apurinic/apyrimidinic endonu...BACKGROUND Colorectal cancer(CRC)is a common malignant tumor of the digestive tract worldwide,characterized by high incidence and mortality rates.AIM To investigate the expression of serum apurinic/apyrimidinic endonuclease 1 autoantibodies(APE1-AAbs),peripheral pentraxin-3(PTX-3),and miR-486-3p in patients with CRC undergoing radical surgery and their relationship with postoperative recurrence and metastasis.METHODS A retrospective analysis was conducted on the clinical data of 154 CRC patients who underwent laparoscopic radical surgery in our hospital from January 2022 to January 2024.Patients were followed for one year postoperatively and divided into an occurrence group(n=28)and a non-occurrence group(n=126)based on whether they experienced recurrence or metastasis.The clinical data and the expression levels of APE1-AAbs,PTX-3,and miR-486-3p were compared between the two groups.Multivariate logistic regression analysis was performed to identify risk factors for postoperative recurrence and metastasis in CRC patients.The relationship of APE1-AAbs,PTX-3,and miR-486-3p with postoperative recurrence and metastasis was analyzed using Spearman correlation analysis.Receiver operating characteristic curves were drawn to evaluate the predictive value of serum APE1-AAbs,PTX-3,and miR-486-3p levels alone and their combination for postoperative recurrence and metastasis in CRC.RESULTS The occurrence group had significantly higher proportions of patients with an age≥60 years,lymph node metastasis,stage III disease,poor differentiation,tumor diameter>5 cm,and higher platelet count,carcinoembryonic antigen,and carbohydrate antigen 19-9 levels than the non-occurrence group(P<0.05).The expression levels of APE1-AAbs,PTX-3,and miR-486-3p in the occurrence group were significantly higher than those in the non-occurrence group(P<0.05).Multivariate logistic regression analysis showed that lymph node metastasis,stage III disease,poor differentiation,and elevated levels of APE1-AAbs,PTX-3,and miR-486-3p were risk factors for postoperative recurrence and metastasis in CRC patients(odds ratio>1,P<0.05).Spearman correlation analysis revealed that the levels of APE1-AAbs,PTX-3,and miR-486-3p were positively correlated with postoperative recurrence and metastasis in CRC patients(r=0.642,0.653,and 0.631,respectively,P<0.05).Receiver operating characteristic curve analysis showed that the area under the curve values for APE1-AAbs,PTX-3,and miR-486-3p levels alone and their combination in predicting postoperative recurrence and metastasis in CRC were 0.764,0.783,0.806,and 0.875,respectively,with the combination significantly outperforming individual markers(P<0.05).CONCLUSION Serum APE1-AAbs,PTX-3,and miR-486-3p levels are higher in CRC patients with postoperative recurrence and metastasis.These three markers are risk factors for postoperative recurrence and metastasis in CRC and can be used as predictive biomarkers.The combined detection of these markers has higher predictive value compared to individual tests.展开更多
基金Supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBJC00001the Key Discipline Special Project of Tianjin Municipal Health Commission,No.TJWJ2022XK016.
文摘BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.
文摘BACKGROUND Colorectal cancer(CRC)is a common malignant tumor of the digestive tract worldwide,characterized by high incidence and mortality rates.AIM To investigate the expression of serum apurinic/apyrimidinic endonuclease 1 autoantibodies(APE1-AAbs),peripheral pentraxin-3(PTX-3),and miR-486-3p in patients with CRC undergoing radical surgery and their relationship with postoperative recurrence and metastasis.METHODS A retrospective analysis was conducted on the clinical data of 154 CRC patients who underwent laparoscopic radical surgery in our hospital from January 2022 to January 2024.Patients were followed for one year postoperatively and divided into an occurrence group(n=28)and a non-occurrence group(n=126)based on whether they experienced recurrence or metastasis.The clinical data and the expression levels of APE1-AAbs,PTX-3,and miR-486-3p were compared between the two groups.Multivariate logistic regression analysis was performed to identify risk factors for postoperative recurrence and metastasis in CRC patients.The relationship of APE1-AAbs,PTX-3,and miR-486-3p with postoperative recurrence and metastasis was analyzed using Spearman correlation analysis.Receiver operating characteristic curves were drawn to evaluate the predictive value of serum APE1-AAbs,PTX-3,and miR-486-3p levels alone and their combination for postoperative recurrence and metastasis in CRC.RESULTS The occurrence group had significantly higher proportions of patients with an age≥60 years,lymph node metastasis,stage III disease,poor differentiation,tumor diameter>5 cm,and higher platelet count,carcinoembryonic antigen,and carbohydrate antigen 19-9 levels than the non-occurrence group(P<0.05).The expression levels of APE1-AAbs,PTX-3,and miR-486-3p in the occurrence group were significantly higher than those in the non-occurrence group(P<0.05).Multivariate logistic regression analysis showed that lymph node metastasis,stage III disease,poor differentiation,and elevated levels of APE1-AAbs,PTX-3,and miR-486-3p were risk factors for postoperative recurrence and metastasis in CRC patients(odds ratio>1,P<0.05).Spearman correlation analysis revealed that the levels of APE1-AAbs,PTX-3,and miR-486-3p were positively correlated with postoperative recurrence and metastasis in CRC patients(r=0.642,0.653,and 0.631,respectively,P<0.05).Receiver operating characteristic curve analysis showed that the area under the curve values for APE1-AAbs,PTX-3,and miR-486-3p levels alone and their combination in predicting postoperative recurrence and metastasis in CRC were 0.764,0.783,0.806,and 0.875,respectively,with the combination significantly outperforming individual markers(P<0.05).CONCLUSION Serum APE1-AAbs,PTX-3,and miR-486-3p levels are higher in CRC patients with postoperative recurrence and metastasis.These three markers are risk factors for postoperative recurrence and metastasis in CRC and can be used as predictive biomarkers.The combined detection of these markers has higher predictive value compared to individual tests.
