Vulvar cancer is the fourth most common gynecological malignancy,with a global incidence of an estimated 45,240 new cases and 17,427 deaths in 2022.1 The 5-year survival rate for vulvar cancer is about 70%based on dat...Vulvar cancer is the fourth most common gynecological malignancy,with a global incidence of an estimated 45,240 new cases and 17,427 deaths in 2022.1 The 5-year survival rate for vulvar cancer is about 70%based on data from the SEER database.2 More than 90%of vulvar cancer was vulvar squamous cell carcinoma(SCC),which included keratinizing,non-keratinizing,basaloid,warty,and verrucous carcinoma.展开更多
The dysregulation of exosomal microRNAs(miRNAs)plays a crucial role in the development and progression of cancer.This study investigated the role of a newly identified serum exosomal miRNA miR-4256 in gastric cancer(G...The dysregulation of exosomal microRNAs(miRNAs)plays a crucial role in the development and progression of cancer.This study investigated the role of a newly identified serum exosomal miRNA miR-4256 in gastric cancer(GC)and the underlying mechanisms.The differentially expressed miRNAs were firstly identified in serum exosomes of GC patients and healthy individuals using next-generation sequencing and bioinformatics.Next,the expression of serum exosomal miR-4256 was analyzed in GC cells and GC tissues,and the role of miR-4256 in GC was investigated by in vitro and in vivo experiments.Then,the effect of miR-4256 on its downstream target genes HDAC5/p16^(INK4a) was studied in GC cells,and the underlying mechanisms were evaluated using dual luciferase reporter assay and Chromatin Immunoprecipitation(ChIP).Additionally,the role of the miR-4256/HDAC5/p16^(INK4a) axis in GC was studied using in vitro and in vivo experiments.Finally,the upstream regulators SMAD2/p300 that regulate miR-4256 expression and their role in GC were explored using in vitro experiments.miR-4256 was the most significantly upregulated miRNA and was overexpressed in GC cell lines and GC tissues;in vitro and in vivo results showed that miR-4256 promoted GC growth and progression.Mechanistically,miR-4256 enhanced HDAC5 expression by targeting the promoter of the HDAC5 gene in GC cells,and then restrained the expression of p16^(INK4a) through the epigenetic modulation of HDAC5 at the p16INK4a promoter.Furthermore,miR-4256 overexpression was positively regulated by the SMAD2/p300 complex in GC cells.Our data indicate that miR-4256 functions as an oncogene in GC via the SMAD2/miR-4256/HDAC5/p16^(INK4a) axis,which participates in GC progression and provides novel therapeutic and prognostic biomarkers for GC.展开更多
目的探讨P16^(INK4a)与Ki67两个辅助指标对宫颈上皮病变诊断准确性的影响。方法选取2015年1月—2018年8月于本院经病理诊断为宫颈上皮病变(cervical intra epithelial neoplasia,CIN)的患者90例,所有患者的宫颈组织切片均行石蜡包埋,并...目的探讨P16^(INK4a)与Ki67两个辅助指标对宫颈上皮病变诊断准确性的影响。方法选取2015年1月—2018年8月于本院经病理诊断为宫颈上皮病变(cervical intra epithelial neoplasia,CIN)的患者90例,所有患者的宫颈组织切片均行石蜡包埋,并进行CINⅠ~Ⅲ分级,采用SP法分别进行P16^(INK4a)和Ki67的免疫组化染色并检测其表达。结果P16^(INK4a)、Ki67的阳性表达率随CIN级别升高而升高,两者在CINⅠ~Ⅲ级中的阳性表达差异有统计学意义(P<0.05),P16^(INK4a)阳性表达率均与CIN病变级别呈正相关(r1=0.703,P<0.05);Ki67阳性表达率与CIN病变级别呈正相关(r2=0.697,P<0.05)。在CINⅠ~Ⅲ中P16^(INK4a)与Ki67的阳性表达具有相关性(r=0.715,P<0.05)。结论P16^(INK4a)和Ki67联合免疫组化检测能有效提高宫颈上皮病变病理学诊断的一致性和准确性,同时结合组织学检查,能更好地提高筛查的准确性,有助于个体化治疗方案的制定。展开更多
基金supported by the National Natural Science Foundation of China(No.82125012,91849208)the National Key Research and Development Program of China(No.2021ZD0202400)。
基金supported by the Tai-Shan Scholar Program of Shandong Province (Code:ts20070743)Beijing Hospitals Authority's Ascent Plan (Code:DFL20221201).
文摘Vulvar cancer is the fourth most common gynecological malignancy,with a global incidence of an estimated 45,240 new cases and 17,427 deaths in 2022.1 The 5-year survival rate for vulvar cancer is about 70%based on data from the SEER database.2 More than 90%of vulvar cancer was vulvar squamous cell carcinoma(SCC),which included keratinizing,non-keratinizing,basaloid,warty,and verrucous carcinoma.
基金The studies involving human participants were approved by The First Affiliated Hospital of Jinan University Ethics Committee(KY-2021-095)The participants provided their written informed consent to participate in this study+1 种基金Animalinvolved experimental protocols were compliance with guidelines and licensesapproved by the Laboratory Animal Center of Jinan University(20220225-65).
文摘The dysregulation of exosomal microRNAs(miRNAs)plays a crucial role in the development and progression of cancer.This study investigated the role of a newly identified serum exosomal miRNA miR-4256 in gastric cancer(GC)and the underlying mechanisms.The differentially expressed miRNAs were firstly identified in serum exosomes of GC patients and healthy individuals using next-generation sequencing and bioinformatics.Next,the expression of serum exosomal miR-4256 was analyzed in GC cells and GC tissues,and the role of miR-4256 in GC was investigated by in vitro and in vivo experiments.Then,the effect of miR-4256 on its downstream target genes HDAC5/p16^(INK4a) was studied in GC cells,and the underlying mechanisms were evaluated using dual luciferase reporter assay and Chromatin Immunoprecipitation(ChIP).Additionally,the role of the miR-4256/HDAC5/p16^(INK4a) axis in GC was studied using in vitro and in vivo experiments.Finally,the upstream regulators SMAD2/p300 that regulate miR-4256 expression and their role in GC were explored using in vitro experiments.miR-4256 was the most significantly upregulated miRNA and was overexpressed in GC cell lines and GC tissues;in vitro and in vivo results showed that miR-4256 promoted GC growth and progression.Mechanistically,miR-4256 enhanced HDAC5 expression by targeting the promoter of the HDAC5 gene in GC cells,and then restrained the expression of p16^(INK4a) through the epigenetic modulation of HDAC5 at the p16INK4a promoter.Furthermore,miR-4256 overexpression was positively regulated by the SMAD2/p300 complex in GC cells.Our data indicate that miR-4256 functions as an oncogene in GC via the SMAD2/miR-4256/HDAC5/p16^(INK4a) axis,which participates in GC progression and provides novel therapeutic and prognostic biomarkers for GC.
文摘目的探讨P16^(INK4a)与Ki67两个辅助指标对宫颈上皮病变诊断准确性的影响。方法选取2015年1月—2018年8月于本院经病理诊断为宫颈上皮病变(cervical intra epithelial neoplasia,CIN)的患者90例,所有患者的宫颈组织切片均行石蜡包埋,并进行CINⅠ~Ⅲ分级,采用SP法分别进行P16^(INK4a)和Ki67的免疫组化染色并检测其表达。结果P16^(INK4a)、Ki67的阳性表达率随CIN级别升高而升高,两者在CINⅠ~Ⅲ级中的阳性表达差异有统计学意义(P<0.05),P16^(INK4a)阳性表达率均与CIN病变级别呈正相关(r1=0.703,P<0.05);Ki67阳性表达率与CIN病变级别呈正相关(r2=0.697,P<0.05)。在CINⅠ~Ⅲ中P16^(INK4a)与Ki67的阳性表达具有相关性(r=0.715,P<0.05)。结论P16^(INK4a)和Ki67联合免疫组化检测能有效提高宫颈上皮病变病理学诊断的一致性和准确性,同时结合组织学检查,能更好地提高筛查的准确性,有助于个体化治疗方案的制定。
