MiRNA-145-5p inhibits gastric cancer progression via the serpin family E member 1-extracellular signal-regulated kinase-1/2 axis

BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.

血浆丝氨酸蛋白酶抑制剂E1蛋白水平与幽门螺杆菌感染的关系研究

目的:探讨人体血浆丝氨酸蛋白酶抑制剂E1(serpin peptidase inhibitor clade E member 1,SERPINE1)蛋白水平与幽门螺杆菌(Helicobacter pylori,Hp)感染的关系,为Hp相关性胃癌的机制研究提供理论依据。方法:纳入417名受试者,分为Hp阴性组(192例)以及Hp阳性组(225例),检测受试者血浆生化指标及SERPINE1蛋白水平。结果:Hp阴性组、Hp阳性组中受试者血浆SERPINE1蛋白水平分别为5.38(4.56~6.18)(ng/mL)、8.20(6.91~9.34)(ng/mL),差异具有统计学意义(P<0.01);依据血浆SERPINE1蛋白水平的四分位数间距对受试者进行分组,相关性分析显示随着血浆SERPINE1蛋白水平的升高,Hp感染率也逐步升高(P<0.001);血浆SERPINE1蛋白水平构建诊断Hp感染的受试者工作曲线(Receive operating characteristic curve,ROC),其曲线下面积为0.906,且最佳截点值为6.49ng/mL,诊断Hp感染的灵敏度为84.4%,特异度为83.3%。结论:血浆SERPINE1蛋白水平与Hp感染具有一定的相关性,SERPINE1蛋白可能在Hp相关性胃癌发生发展中具有重要作用。

Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma

Hypoxia,as an important hallmark of the tumor microenvironment,is a major cause of oxidative stress and plays a central role in various malignant tumors,including glioblastoma.Elevated reactive oxygen species(ROS)in a hypoxic microenvironment promote glioblastoma progression;however,the underlying mechanism has not been clarified.Herein,we found that hypoxia promoted ROS production,and the proliferation,migration,and invasion of glioblastoma cells,while this promotion was restrained by ROS scavengers N-acetyl-L-cysteine(NAC)and diphenyleneiodonium chloride(DPI).Hypoxia-induced ROS activated hypoxia-inducible factor-1α(HIF-1α)signaling,which enhanced cell migration and invasion by epithelial-mesenchymal transition(EMT).Furthermore,the induction of serine protease inhibitor family E member 1(SERPINE1)was ROS-dependent under hypoxia,and HIF-1αmediated SERPINE1 increase induced by ROS via binding to the SERPINE1 promoter region,thereby facilitating glioblastoma migration and invasion.Taken together,our data revealed that hypoxia-induced ROS reinforce the hypoxic adaptation of glioblastoma by driving the HIF-1α-SERPINE1 signaling pathway,and that targeting ROS may be a promising therapeutic strategy for glioblastoma.

纤溶酶原激活物抑制剂-1在术后粘连中研究现状

纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor-1,PAI-1)又称丝氨酸蛋白酶抑制剂E1(serpin peptidase inhibitor clade E member 1,SerpinE1)是丝氨酸蛋白酶抑制剂超家族的成员之一,由SERPINE1基因编码。PAI-1在生理水平抑制纤维蛋白溶解活性,参与伤口愈合、基质重建、细胞迁移、细胞增殖和分化等过程。而PAI-1在病理水平通过影响纤溶系统、相关炎症因子、调节信号通路,与术后粘连密切相关。本文就PAI-1在体内的生理作用、伤口愈合时术后粘连的形成过程、PAI-1在术后粘连中的作用及机制作一综述。

Reduced cell invasion may be a characteristic of placental defects in pregnant women of advanced maternal age at single-cell level

The mechanisms underlying pregnancy complications caused by advanced maternal age(AMA)remain unclear.We analyzed the cellular signature and transcriptomes of human placentas in AMA women to elucidate these mechanisms.Placental tissues from two AMA women and two controls were used for single-cell RNA-sequencing(scRNA-seq).Controls consisted of AMA women who did not experience any pregnancy complications and pregnant women below the age of 35 years without pregnancy complications.Trophoblast cells were obtained from the placentas of another six pregnant women(three AMA women and three controls),and in-vitro transwell assays were conducted to observe the cell invasion ability.Thirty additional samples(from 15 AMA women and 15 controls)were analyzed to verify the specific expression of serine protease inhibitor clade E member 1(SERPINE1).Preliminary study of the role of SERPINE1 in cell invasion was carried out with HTR8-S/Vneo cells.High-quality transcriptomes of 27607 cells were detected.Three types of trophoblast cells were detected,which were further classified into eight subtypes according to differences in gene expression and Gene Ontology(GO)function.We identified 110 differentially expressed genes(DEGs)in trophoblast cells between the AMA and control groups,and the DEGs were enriched in multiple pathways related to cell invasion.In-vitro transwell assays suggested that the invading trophoblast cells in AMA women were reduced.SERPINE1 was specifically expressed in the trophoblast,and its expression was higher in AMA women(P<0.05).Transfection of human SERPINE1(hSERPINE1)into HTR8-S/Vneo trophoblast cells showed fewer invading cells in the hSERPINE1 group.Impaired cell invasion may underlie the increased risk of adverse pregnancy outcomes in AMA women.Abnormal expression of SERPINE1 in extravillous trophoblast(EVT)cells appears to play an important role.