miRNA-4295/ST18轴在乳腺癌发生中的作用及对乳腺癌早期筛查诊断的临床价值  

The role of miRNA-4295/ST18 axis in the occurrence of breast cancer and its clinical value for early screening and diagnosis of breast cancer

作　　者：徐艳敏 张玲玲 马秀凤 XU Yanmin;ZHANG Lingling;MA Xiufeng(Department of Surgery,Hongqi Hospital Affiliated to Mudanjiang Medical University,Heilongjiang Mudanjiang 157000,China)

机构地区：[1]牡丹江医学院附属红旗医院外科,黑龙江牡丹江157000

出　　处：《现代肿瘤医学》2023年第13期2455-2462,共8页Journal of Modern Oncology

基　　金：黑龙江省省属高校基本科研项目(编号:2020-KYYwFMY-0022)。

摘　　要：目的:探讨微小RNA-4295(miRNA-4295)/肿瘤抑制子18(ST18)轴在乳腺癌发生中的作用及对乳腺癌早期筛查诊断的临床价值。方法:采用GeneChip®技术筛选与乳腺癌相关差异miRNAs谱系,实时荧光定量PCR进行验证;Transwell实验和流式细胞仪评估乳腺癌细胞的迁移和凋亡情况;生物信息学分析和双荧光素酶报告实验寻找miRNA下游靶标;并对生物标志物用于诊断乳腺癌的效能进行评价。结果:miRNA-4295高表达于乳腺癌组织中;过表达miRNA-4295促进乳腺癌细胞迁移,而抑制miRNA-4295表达减少乳腺癌细胞迁移、诱导乳腺癌细胞凋亡;双荧光素酶实验证实ST18是miRNA-4295下游靶标,转染ST18野生型质粒抑制乳腺癌细胞迁移并诱导乳腺癌细胞凋亡,逆转miRNA-4295的作用效应。miRNA-4295与CA153、CEA联合检测对乳腺癌诊断效能显著优于CA153、CEA和miRNA-4295单项检测(均P<0.05),联合检测诊断乳腺癌的受试者工作特征曲线(ROC)下面积为0.775。结论:miRNA-4295通过靶向调控ST18参与乳腺癌的发生发展;miRNA-4295与CA153、CEA联合检测能够显著提高乳腺癌早期筛查诊断效能,对于乳腺癌的早期筛查诊断具有重要临床价值。Objective:To explore the mechanism of micro RNA-4295(miRNA-4295)/suppression of tumorigenicity 18(ST18)axis in the occurrence of breast cancer,and its clinical value in early screening and diagnosis of breast cancer.Methods:GeneChip® technology was used to screen the difference of miRNAs spectrum for breast cancer.Real time quantitative PCR was used to verify the difference miRNAs.Transwell assay and flow cytometry analysis were used to evaluate the migration and apoptosis of breast cancer cells.Bioinformatics analysis and double luciferase reporting experiment to find miRNA downstream targets.The efficacy of biomarkers in the diagnosis of breast cancer was compared.Results:miRNA-4295 was highly expressed in breast cancer tissues.Overexpression of miRNA-4295 promotes breast cancer cell migration,however,inhibition of miRNA-4295 reduces migrationand induces apoptosis of breast cancer cells.Double luciferase experiment confirmed that ST18 was the downstream target of miRNA-4295.Transfection of ST18 wild type plasmid inhibits migration and induces apoptosis of breast cancer cells,reversing the effect of miRNA-4295.The combined detection of miRNA-4295,CA153 and CEA was significantly superior to the single detection of CA153,CEA and miRNA-4295(all P<0.05)in the diagnosis of breast cancer.The area under the ROC curve of the combined detection was 0.775.Conclusion:miRNA-4295 participates in the occurrence and development of breast cancer by targeting ST18.The combined detection of miRNA-4295,CA153 and CEA can significantly improve the efficiency of early screening and diagnosis of breast cancer,and has important clinical value for early screening and diagnosis of breast cancer.

关 键 词：乳腺癌 微小RNA-4295(miRNA-4295) 肿瘤抑制子18(ST18) 机制 早期筛查 诊断 

分 类 号：R737.9[医药卫生—肿瘤]