Long non-coding RNA-ATB induces trastuzumab resistance and aggravates the progression of gastric cancer by repressing miR- 200c via ZNF217 elevation

Background: Trastuzumab resistance accounts for chemotherapy failure in gastric cancer patients in clinicalpractice. The significance of long non-coding RNAs (lncRNAs) in the maintenance of drug resistance in gastriccancer has been already underlined. Method: This study aimed to identify the specific role of lncRNA-ATB in gastriccancer progression and trastuzumab resistance. The downstream miRs of lncRNA-ATB and target genes of miRs werepredicted by bioinformatics analysis and verified using dual luciferase reporter assay. Loss- and gain-function assayswere performed to explore the roles of lncRNA-ATB, miR-200c, and zinc-finger protein 217 (ZNF217) in the cellfunctions and trastuzumab resistance of a trastuzumab-resistant gastric cancer cell line (NCI-N87-TR). Result:LncRNA-ATB was upregulated, while miR-200c was downregulated. Depletion of lncRNA-ATB or miR-200celevation led to a decrease in malignant properties of NCI-N87-TR cells. LncRNA-ATB could negatively target miR-200c, which in turn inversely targeted and reduced the expression of ZNF217. Silencing of ZNF217 could inhibit cellviability and migration. Conclusion: lncRNA-ATB promoted the progression and trastuzumab resistance of gastriccancer by repressing miR-200c via ZNF217 upregulation.

孕中期唐氏筛查血清标志物及miR-200C与病理妊娠的关系

目的探究孕中期唐氏筛查血清中甲胎蛋白(AFP)、人绒毛膜促性腺激素(β-h CG)、游离雌三醇(u E3)及微小RNA200C(miR-200C)与病理妊娠的关系。方法回顾性选择862例孕中期妊娠者作为研究对象,收集所有研究对象血清。采用时间分辨荧光法测定血清中AFP、β-h CG、u E3水平,RT-PCR法检测血清中miR-200C水平。根据血清标志物中位数值的倍数(MOM)值、miR-200C平均值进行分组,对比不同水平AFP、β-h CG、u E3、miR-200C病理妊娠发生情况。Logistic多因素回归性分析血清检测指标与病理妊娠的相关性,创建受试者工作特征曲线(ROC)对比不同指标曲线下面积(AUC)。结果 102例妊娠者发生病理妊娠,占11.83%,主要包括胎膜早破、妊娠期糖尿病、妊娠期高血压、早产以及胎儿先天畸。AFP、β-h CG升高组、u E3降低组以及miR-200C高表达组在胎膜早破、妊娠期糖尿病、妊娠期高血压、早产、胎儿先天畸形病理妊娠中发生率高于正常组,差异有统计学意义(P<0.05)。Logistic多因素回归性分析显示病理妊娠的发生与血清AFP、β-h CG、u E3、miR-200C均具有显著相关性(OR=1.536,1.732,1.248,1.671,P<0.05)。ROC曲线分析显示,AFP、β-h CG、u E3、miR-200C预测病理妊娠AUC值分别为0.782、0.869、0.806、0.713,其中β-h CG预测价值最高。结论孕中期血清AFP、β-h CG、miR-200C升高,u E3降低与病理妊娠的发生相关,推测其可作为病理妊娠的预测指标。

母体血液指标miR-200C、hsA-miR-124A-3p与常规血清标志物在孕中期唐氏综合征筛查中的随机对照研究

目的探究母体血液指标微小RNA200C(miR-200C)、hsA-miR-124A-3p与常规血清标志物在孕中期唐氏综合征(DS)筛查中的临床价值。方法选取我院2015年1月~2020年6月孕中期(14~27w)DS孕妇55例作为观察组,按照1:1原则随机选取正常妊娠孕妇55例作为对照组。比较两组一般资料、母体血液指标miR-200C、hsA-miR-124A-3p、常规血清标志物[游离雌三醇(uE_(3))、人绒毛膜促性腺激素(β-hCG)、甲胎蛋白(AFP)]MOM值,分析血浆miR-200C、hsA-miR-124A-3p与血清uE_(3)、β-hCG、AFP相关性及各指标与DS的关系,评价miR-200C、hsA-miR-124A-3p、血清uE_(3)、β-hCG、AFP对DS的诊断价值。结果两组文化程度、既往吸烟、饮酒、规律服用叶酸、孕期接触放射性物质比较,差异有统计学意义(P<0.05)。观察组血浆miR-200C、hsA-miR-124A-3p、血清β-hCG、AFP MOM值高于对照组,血清uE_(3) MOM值低于对照组(P<0.05)。血浆miR-200C、hsA-miR-124A-3p与血清β-hCG、AFP MOM值呈正相关,与uE_(3) MOM值呈负相关(P<0.05)。血浆miR-200C、hsA-miR-124A-3p、血清uE_(3)、β-hCG、AFP与DS发生显著相关(P<0.05)。miR-200C+hsA-miR-124A-3p诊断DS的AUC高于uE_(3)+β-hCG+AFP诊断,且敏感度、特异度分别为78.18%、87.27%。结论母体血液指标miR-200C、hsA-miR-124A-3p联合对DS的诊断效能优于常规血清标志物,可为孕中期DS筛查提供一种新途径,具有较高临床应用价值。