胃癌组织中CPT1C、SERPINH1表达与卵巢转移的关系研究

目的探讨胃癌组织中肉碱棕榈酰转移酶1C(CPT1C)、Serpin肽酶抑制剂clade H成员1(SERPINH1)表达与卵巢转移的关系。方法选择2021年12月至2023年6月该院收治的286例胃癌患者,其中卵巢转移37例(转移组),无卵巢转移249例(无转移组)。取手术切除的胃癌以及癌旁组织,采用实时定量反转录-聚合酶链反应(RT-PCR)检测CPT1C、SERPINH1表达,采用多因素Logistic回归分析胃癌卵巢转移的影响因素,采用受试者工作特征(ROC)曲线分析CPT1C、SERPINH1预测胃癌卵巢转移的价值。结果胃癌组织中CPT1C、SERPINH1表达高于癌旁组织(P<0.05)。低分化、T3~T4分期、N2~N3分期、CA125水平升高的胃癌患者胃癌组织中CPT1C、SERPINH1表达高于中高分化、T1~T2分期、N0~N1分期、无CA125水平升高的胃癌患者(P<0.05)。转移组CPT1C、SERPINH1表达高于无转移组(P<0.05)。印戒细胞癌、N2~N3分期、CPT1C高表达、SERPINH1高表达是胃癌卵巢转移的危险因素(P<0.05)。CPT1C、SERPINH1预测胃癌卵巢转移的曲线下面积(AUC)分别为0.777(95%CI:0.724~0.824)、0.799(95%CI:0.748~0.844),CPT1C与SERPINH1并联预测胃癌卵巢转移的AUC为0.902(95%CI:0.861~0.934),高于CPT1C、SERPINH1单项预测(P<0.05)。结论胃癌组织中CPT1C、SERPINH1表达与卵巢转移有关,CPT1C、SERPINH1联合检测可预测卵巢转移风险。

SERPINH1 promoted the proliferation and metastasis of colorectal cancer by activating PI3K/Akt/mTOR signaling pathway

BACKGROUND Serpin peptidase inhibitor clade H member 1(SERPINH1)was initially recognized as an oncogene implicated in various human malignancies.Nevertheless,the clinical relevance and functional implications of SERPINH1 in colorectal cancer(CRC)remain largely elusive.AIM To investigate the effects of SERPINH1 on CRC cells and its specific mechanism.METHODS Quantitative real-time polymerase chain reaction,western blotting analysis,The Cancer Genome Atlas data mining and immunohistochemistry were employed to examine SERPINH1 expression in CRC cell lines and tissues.A series of in-vitro assays were performed to demonstrate the function of SERPINH1 and its possible mechanisms in CRC.RESULTS SERPINH1 demonstrated elevated expression levels in both CRC cells and tissues,manifested at both mRNA and protein tiers.Elevated SERPINH1 levels correlated closely with advanced T stage,lymph node involvement,and distant metastasis,exhibiting a significant association with poorer overall survival among CRC patients.Subsequent investigations unveiled that SERPINH1 overexpression notably bolstered CRC cell proliferation,invasion,and migration in vitro,while conversely,SERPINH1 knockdown elicited the opposite effects.Gene set enrichment analysis underscored a correlation between SERPINH1 upregulation and genes associated with cell cycle regulation.Our findings underscored the capacity of heightened SERPINH1 levels to expedite G1/S phase cell cycle progression via phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway activation,thereby facilitating CRC cell invasion and migration.CONCLUSION These findings imply a crucial involvement of SERPINH1 in the advancement and escalation of CRC,potentially positioning it as a novel candidate for prognostic assessment and therapeutic intervention in CRC management.

SERPINE1在胃癌中的表达及对胃癌细胞免疫逃逸和β-catenin/N-cadherin信号通路的作用机制研究

目的 探讨丝氨酸蛋白酶抑制剂E1(SERPINE1)在胃癌中的表达及对胃癌细胞免疫逃逸及β-连环蛋白/神经钙黏蛋白(β-catenin/N-cadherin)信号通路的作用机制。方法 选择2020年1月至2022年1月在定州市人民医院接受胃癌手术的78例患者作为研究对象,收集其胃癌组织及癌旁组织,采用免疫组织化学法检测组织中SERPINE1表达情况。采用人胃癌细胞系SGC-7901细胞,经不同处理后分为对照组(SGC-7901细胞)、oe-SERPINE1组(pcDNA3.1-SERPINE1载体)、oe-NC组(空pcDNA3.1载体)、SERPINE1 siRNA组(SERPINE1 siRNA)及si-NC组(si-NC)。采用实时荧光定量PCR法检测各组细胞中SERPINE1 mRNA的表达水平,采用Transwell法检测各组细胞的侵袭数目,采用划痕实验检测各组细胞的迁移距离,采用蛋白质印迹法检测各组细胞中程序性死亡受体-1(PD-1)、程序性死亡配体-1(PD-L1)、β-catenin、N-cadherin的蛋白表达水平。结果 胃癌组织和癌旁组织中SERPINE1阳性表达率分别为88.46%和19.23%,差异有统计学意义(P<0.05)。oe-NC组细胞的SERPINE1 mRNA表达水平、侵袭数目、迁移距离,以及PD-1、PD-L1、β-catenin、N-cadherin蛋白表达水平与对照组差异均无统计学意义(P均>0.05)。oe-SERPINE1组细胞的上述指标均较oe-NC组显著升高(P均<0.05)。si-NC组细胞的上述指标均较oe-SERPINE1组显著降低(P均<0.05)。SERPINE1siRNA组细胞的上述指标均较si-NC组显著降低(P均<0.05)。结论 SERPINE1在胃癌组织中呈高表达,下调SERPINE1表达可显著抑制胃癌细胞的侵袭和迁移,抑制PD-1、PD-L1表达从而阻止肿瘤细胞发生免疫逃逸,这与抑制β-catenin/N-cadherin信号通路的活性相关。

SerpinE2在细胞外基质代谢中作用的研究进展

丝氨酸蛋白酶抑制剂Ｅ２（ｓｅｒｐｉｎｐｅｐｔｉｄａｓｅｉｎｈｉｂｉｔｏｒｃｌａｄｅＥｍｅｍｂｅｒ２，ＳｅｒｐｉｎＥ２），又称蛋白酶连结蛋白１（ｐｒｏｔｅａｓｅｎｅｘｉｎ１，ＰＮ１），最初被鉴定为神经胶质源性连接蛋白［１］。ＳｅｒｐｉｎＥ２是丝氨酸蛋白酶抑制剂超家族的一员，可以抑制凝血酶、尿激酶、纤溶酶和胰蛋白酶等蛋白酶活性。ＳｅｒｐｉｎＥ２由人染色体２ｑ９９～ｑ３５上的ＳＥＲＰＩＮＥ２基因编码［２］，是一类可以分泌到细胞外基质（ｅｘｔｒａｃｅｌｌｕｌａｒｍａｔｒｉｘ，ＥＣＭ）的蛋白质。大量研究发现，ＳｅｒｐｉｎＥ２可通过调节纤溶酶原激活物和基质金属蛋白酶（ｍａｔｒｉｘｍｅｔａｌｌｏｐｒｏｔｅｉｎａｓｅｓ，ＭＭＰｓ）的活性或表达量从而影响细胞外基质蛋白的代谢。

Clinical significance and role of up-regulation of SERPINA3 expression in endometrial cancer

BACKGROUND Serpin peptidase inhibitor,clade A member 3(SERPINA3)belongs to the serpin family with an inhibitory activity against proteases.Its aberrant expression has been observed in a wide range of tumor cells.However,its clinical significance and biological function in endometrial cancer have been rarely studied.We designed a study to determine the levels of SERPINA3 and its significance in patients with endometrial cancer.AIM To investigate the clinical significance and role of SERPINA3 expression in endometrial cancer cells.METHODS Eighty endometrial tissue samples collected from patients with endometrial cancer were included in an observation group and 80 paraffin-embedded tissues samples collected from patients with normal endometrial tissues undergoing myomectomy were employed as a control group between January 2014 and December 2018.The expression of SERPINA3 mRNA was detected by quantitative polymerase chain reaction(PCR)for all endometrial tissues included in the study.RESULTS The positive expression rate of SERPINA3 protein in endometrial cancer cells was 71.25%in the observation group,which was significantly higher than that in the control group(31.25%;P<0.05).There was no correlation between SERPINA3 protein in endometrial cancer cells and the age range at which women experienced menopause(P>0.05).However,it was associated with pathological grade,clinical stage,vascular invasion,and lymph node metastasis(P<0.05).Pathological grade,clinical stage,vascular invasion,and lymph node metastasis were independent prognostic factors for endometrial cancer.CONCLUSION The follow-up study of SERPINA3 can be used as a prognostic biomarker for endometrial cancer and as one of the targets for bio-targeted therapy for endometrial cancer.

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.

间-α胰蛋白酶抑制因子重链H1、α-2抗纤溶酶、运甲状腺素蛋白对肝纤维化的诊断价值及复方汉防己对其影响

目的：探讨间-α胰蛋白酶抑制因子重链H1（ITIH1）、α-2抗纤溶酶（SERPINF2）、运甲状腺素蛋白（TTR）对大鼠肝纤维化的诊断价值；以及复方汉防己对肝纤维化ITIH1、SERPINF2、TTR的影响。方法；Fisher344大鼠随机分为对照组，造模组，低、中、高剂量复方汉防己干预组。采用RT-PCR和免疫组织化学检测大鼠肝组织ITIH1、SERPINF2、TTR的mRNA及蛋白表达，ELISA法检测其血清含量。H-E染色、Masson三色染色、网状纤维染色观察肝纤维化程度。结果：造模组大鼠血清及肝组织中ITIH1、SERPINF2、TTR蛋白和mRNA的表达较对照组显著减少。复方汉防己干预组大鼠血清及肝组织中3者的表达较造模组均有不同程度升高。病理结果也显示复方汉防己干预组大鼠肝纤维化程度均有不同程度减轻。结论：ITIH1、SERPINF2、TTR对肝纤维化的分级诊断及病情监测具有一定的价值；复方汉防己能明显降低CCl4诱导的大鼠肝纤维化程度并能升高ITIH1、SERPINF2、TTR蛋白和mRNA的表达。

丝氨酸蛋白酶抑制剂E2/蛋白酶连结蛋白-1在关节炎中的作用研究现状

丝氨酸蛋白酶抑制剂E2/蛋白酶连结蛋白-1(Serpin E2/PN-1)是丝氨酸蛋白酶抑制剂家族中的一员,可以多种方式影响细胞外基质蛋白的代谢,调节细胞外基质微环境。Serpin E2/PN-1可以参与循环系统、神经系统、心血管系统、呼吸系统、关节病变、肿瘤、纤维化相关疾病生理和病理过程。本文主要综述Serpin E2/PN-1在关节炎中的变化,以及Serpin E2/PN-1对关节炎基质的影响和作用的研究进展。

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.