Background: MicroRNAs (miRNAs) play important roles in modulating gene expression. In cultured mesangial cells, MiR-377 exhibited the greatest change on exposure to high glucose and led to increased fibronectin produc...Background: MicroRNAs (miRNAs) play important roles in modulating gene expression. In cultured mesangial cells, MiR-377 exhibited the greatest change on exposure to high glucose and led to increased fibronectin production in in-vitro diabetic nephropathy. Our aim was to identify the pattern of microRNA-377 changes in human diabetic patients with different stages of diabetic nephropathy. Methods: The study included 45 patients divided into 5 groups;patients with stage 1 & 2 diabetic nephropathy (DN), stage 3 & 4 DN, diabetics without DN, stage 1 & 2 chronic kidney disease (CKD), and stage 3 & 4 CKD. The following tests were done to all patients;serum creatinine, estimated glomerular filtration rate (eGFR), albumin to creatinine ratio, blood sugar, urine analysis, glycated hemoglobin, fundus examination. The RNA was extracted from plasma samples, TaqMan microRNA (miRNA) assays from applied Bio systems were used for analysis of MicroRNA-377. Results: This study found that patients with the highest median of the interquartile range (IQR) of miR-377 were those of group 1 with significant difference between them and all other groups. MiR-377 was significantly correlated with glycated hemoglobin but not with eGFR. Conclusion: Plasma miR-377 is highly significantly increased in human diabetic patients with early rather than late diabetic nephropathy, diabetics without nephropathy, or those at any stage of other causes of CKD. Our findings confirm the role of miR-377 as a potentially novel target in the development of diabetic nephropathy in humans.展开更多
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
文摘目的:探讨microRNA-377(miR-377)与组蛋白甲基转移酶SMYD3在肝癌中的表达规律及与肝癌的相关性.方法:利用实时定量PCR分别检测不同肝组织及肝细胞系中miR-377表达水平,应用实时定量PCR和Western blot分别检测不同肝组织及肝细胞系中SMYD3 mRNA和蛋白水平的表达情况.通过转染miR-377模拟物上调其在肝癌细胞株HepG2中表达后,应用实时定量PCR、Western blot分别检测转染前后HepG2中SMYD3 mRNA和蛋白表达的变化.结果:MiR-377 mRNA在人肝癌旁组织和肝癌组织中的表达较正常肝脏明显降低(0.331±0.059,0.139±0.064 vs 0.874±0.178,均P<0.05);在HepG2中的表达较L-02明显降低(0.145±0.021vs0.868±0.194,P<0.05).SMYD3 mRNA和蛋白质在人肝癌旁组织和肝癌组织中的表达较正常肝脏明显升高(mRNA:3.836±0.137,5.836±0.965vs1.235±0.332;蛋白:0.381±0.020,0.484±0.030vs0.252±0.015;均P<0.05).SMYD3 mRNA和蛋白质在肝癌细胞系HepG2中的表达较正常肝细胞系L-02明显升高(mRNA:0.845±0.047vs0.348±0.134;蛋白:0.575±0.008vs0.259±0.007,均P<0.05).转染miRNA-377模拟物上调HepG2中miR-377表达后转染组SMYD3 mRNA和蛋白表达较空白组和阴性对照组均明显下降(mRNA:0.125±0.010 vs 0.857±0.163,0.779±0.167;蛋白:0.092±0.026 vs 0.347±0.040,0.383±0.054,均P<0.05).结论:miRNA-377在肝癌中表达明显下调,其靶基因SMYD3表达上调;表达下调的miRNA-377丧失对SMYD3表达的抑制可能是肝癌发生的重要机制.
文摘Background: MicroRNAs (miRNAs) play important roles in modulating gene expression. In cultured mesangial cells, MiR-377 exhibited the greatest change on exposure to high glucose and led to increased fibronectin production in in-vitro diabetic nephropathy. Our aim was to identify the pattern of microRNA-377 changes in human diabetic patients with different stages of diabetic nephropathy. Methods: The study included 45 patients divided into 5 groups;patients with stage 1 & 2 diabetic nephropathy (DN), stage 3 & 4 DN, diabetics without DN, stage 1 & 2 chronic kidney disease (CKD), and stage 3 & 4 CKD. The following tests were done to all patients;serum creatinine, estimated glomerular filtration rate (eGFR), albumin to creatinine ratio, blood sugar, urine analysis, glycated hemoglobin, fundus examination. The RNA was extracted from plasma samples, TaqMan microRNA (miRNA) assays from applied Bio systems were used for analysis of MicroRNA-377. Results: This study found that patients with the highest median of the interquartile range (IQR) of miR-377 were those of group 1 with significant difference between them and all other groups. MiR-377 was significantly correlated with glycated hemoglobin but not with eGFR. Conclusion: Plasma miR-377 is highly significantly increased in human diabetic patients with early rather than late diabetic nephropathy, diabetics without nephropathy, or those at any stage of other causes of CKD. Our findings confirm the role of miR-377 as a potentially novel target in the development of diabetic nephropathy in humans.
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.
