In recent years,an increasing number of young women have been diagnosed with cancer,including some nulliparous women.Therefore,many young patients with early-stage cancer desire to preserve fertility after cytotoxic o...In recent years,an increasing number of young women have been diagnosed with cancer,including some nulliparous women.Therefore,many young patients with early-stage cancer desire to preserve fertility after cytotoxic oncological treatments.It is important to develop a multidisciplinary approach to achieve the best outcomes for each patient.On the other hand,there has been a sharp increase in microRNAs(miRNAs)as potential biomarkers for the diagnosis,prognosis,and evaluation of treatment efficacy of several diseases.MiR-543 has been reported to affect the pathogenesis and progression of diseases via complex mechanisms.Understanding the regulatory role of miR-543 may aid comprehension of the pathogenesis and treatment of a broad range of diseases.Therefore,we provide an overview of the biogenesis,function,and role of miR-543 in various systems.These results shed light on the anticancer and endometrial protection role of miR-543 in young patients with gynecologic tumors and highlight the clinical potential of miR-543-based applications and related challenges.展开更多
目的:急性脑梗死病情进展迅速,常导致神经不可逆损伤,预后较差,需寻找相关预后标志物以了解预后情况。本研究旨在分析细胞色素P450(cytochrome P450,CYP)3A5基因多态性联合血清微RNA-543(microRNA-543,miR-543)预测急性脑梗死患者预后...目的:急性脑梗死病情进展迅速,常导致神经不可逆损伤,预后较差,需寻找相关预后标志物以了解预后情况。本研究旨在分析细胞色素P450(cytochrome P450,CYP)3A5基因多态性联合血清微RNA-543(microRNA-543,miR-543)预测急性脑梗死患者预后不良的价值。方法:选取2021年5月至2024年1月在郑州市第七人民医院诊断为急性脑梗死的176例患者作为研究对象,依据患者出院90 d后的门诊改良Rankin量表评分结果,将评分≤2的患者纳入预后良好组(n=92),评分>2的纳入预后不良组(n=84)。采用实时荧光定量PCR法检测治疗前血清miR-543水平,采用PCR法检测治疗前CYP3A5基因型,采用多因素Logistic回归分析影响急性脑梗死患者预后不良的因素,采用受试者操作特征(receiver operating characteristic,ROC)曲线分析CYP3A5基因rs776746位点GG基因型联合血清miR-543水平对急性脑梗死患者预后不良的预测价值。结果:CYP3A5基因rs776746位点上检出AA型、GA型、GG型3种基因型。预后不良组发病至溶栓时间长于预后良好组,血清miR-543水平、携带CYP3A5基因rs776746位点GG基因型及G等位基因、入院时美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分≥15和高血压患者比例均显著高于预后良好组(均P<0.001)。携带CYP3A5基因rs776746位点GG基因型和高miR-543水平是急性脑梗死患者预后不良的危险因素(均P<0.05)。CYP3A5基因rs776746位点GG基因型和血清miR-543水平单独及联合预测急性脑梗死患者预后不良的曲线下面积(area under the curve,AUC)分别为0.702、0.833、0.932,敏感度分别为52.38%、75.68%、92.86%,特异度分别为88.04%、78.33%、93.48%。结论:携带CYP3A5基因rs776746位点GG基因型和高miR-543水平均与急性脑梗死患者预后不良有关,二者联合可显著提高预测效能。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
基金This work was supported by grants from the National Basic Research Program of China(2015CB943304)National Natural Science Foundation ofChina(81671457 and 81871143 to X.YZ,31800768 to W.T.H.).
文摘In recent years,an increasing number of young women have been diagnosed with cancer,including some nulliparous women.Therefore,many young patients with early-stage cancer desire to preserve fertility after cytotoxic oncological treatments.It is important to develop a multidisciplinary approach to achieve the best outcomes for each patient.On the other hand,there has been a sharp increase in microRNAs(miRNAs)as potential biomarkers for the diagnosis,prognosis,and evaluation of treatment efficacy of several diseases.MiR-543 has been reported to affect the pathogenesis and progression of diseases via complex mechanisms.Understanding the regulatory role of miR-543 may aid comprehension of the pathogenesis and treatment of a broad range of diseases.Therefore,we provide an overview of the biogenesis,function,and role of miR-543 in various systems.These results shed light on the anticancer and endometrial protection role of miR-543 in young patients with gynecologic tumors and highlight the clinical potential of miR-543-based applications and related challenges.
文摘目的:急性脑梗死病情进展迅速,常导致神经不可逆损伤,预后较差,需寻找相关预后标志物以了解预后情况。本研究旨在分析细胞色素P450(cytochrome P450,CYP)3A5基因多态性联合血清微RNA-543(microRNA-543,miR-543)预测急性脑梗死患者预后不良的价值。方法:选取2021年5月至2024年1月在郑州市第七人民医院诊断为急性脑梗死的176例患者作为研究对象,依据患者出院90 d后的门诊改良Rankin量表评分结果,将评分≤2的患者纳入预后良好组(n=92),评分>2的纳入预后不良组(n=84)。采用实时荧光定量PCR法检测治疗前血清miR-543水平,采用PCR法检测治疗前CYP3A5基因型,采用多因素Logistic回归分析影响急性脑梗死患者预后不良的因素,采用受试者操作特征(receiver operating characteristic,ROC)曲线分析CYP3A5基因rs776746位点GG基因型联合血清miR-543水平对急性脑梗死患者预后不良的预测价值。结果:CYP3A5基因rs776746位点上检出AA型、GA型、GG型3种基因型。预后不良组发病至溶栓时间长于预后良好组,血清miR-543水平、携带CYP3A5基因rs776746位点GG基因型及G等位基因、入院时美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分≥15和高血压患者比例均显著高于预后良好组(均P<0.001)。携带CYP3A5基因rs776746位点GG基因型和高miR-543水平是急性脑梗死患者预后不良的危险因素(均P<0.05)。CYP3A5基因rs776746位点GG基因型和血清miR-543水平单独及联合预测急性脑梗死患者预后不良的曲线下面积(area under the curve,AUC)分别为0.702、0.833、0.932,敏感度分别为52.38%、75.68%、92.86%,特异度分别为88.04%、78.33%、93.48%。结论:携带CYP3A5基因rs776746位点GG基因型和高miR-543水平均与急性脑梗死患者预后不良有关,二者联合可显著提高预测效能。
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.
