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Arboviruses: Transmission and Host Resistance. 虫媒病毒:传播和宿主抵抗力。
IF 1.6 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-01 DOI: 10.1615/CritRevEukaryotGeneExpr.2023049820
Sidra Anwar, Bilal Ahmed, Muhammad Imran Qadir

In this review, there is a complete description of the classes of arboviruses, their evolutionary process, virus characterization, disease transmission methods; it also describes about the vectors involved in transmission and their mood of transmission, both biologically as well as non-biologically and, about host, the resistance mechanism in host, and artificial methods of preventing those viral transmissions. Arboviruses transmitted to hosts by some vectors such as mosquitoes, ticks, etc. The virus replicates in the host can be prevented by some host resistance mechanisms like RNA interference (RNAi), which degrade virus RNA by its antiviral activity, insect repellents, IGRs, and PI technology.

这篇综述全面介绍了虫媒病毒的种类、进化过程、病毒特征、疾病传播方式;还介绍了参与传播的载体及其生物和非生物传播情绪,以及宿主、宿主的抵抗机制和防止病毒传播的人工方法。虫媒病毒通过蚊子、蜱等载体传播给宿主。病毒在宿主体内的复制可以通过一些宿主抵抗机制来阻止,如 RNA 干扰(RNAi)(通过其抗病毒活性降解病毒 RNA)、驱虫剂、IGRs 和 PI 技术。
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引用次数: 0
Transplantation of miR-193b-3p-Transfected BMSCs Improves Neurological Impairment after Traumatic Brain Injury through S1PR3-Mediated Regulation of the PI3K/AKT/mTOR Signaling Pathway 转染 miR-193b-3p 的 BMSCs 移植通过 S1PR3 介导的 PI3K/AKT/mTOR 信号通路调节改善创伤性脑损伤后的神经功能损伤
IF 1.6 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-01 DOI: 10.1615/critreveukaryotgeneexpr.2024053225
Yinghong He, Yuanmou Li, Yan Zhang, Lixia Chen, Juan Luo, Liqiao Bi, Limei Liu, Xuelian Wang, Meifen Lv
The aim of the present study was to explore the molecular mechanisms by which miR-193b-3p-trans-fected bone marrow mesenchymal stem cells (BMSCs) transplantation improves neurological impairment after traumatic brain injury (TBI) through sphingosine-1-phosphate receptor 3 (S1PR3)-mediated regulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway at the cellular and animal levels. BMSCs were transfected with miR-193b-3p. A TBI cell model was established by oxygen−glucose deprivation (OGD)-induced HT22 cells, and a TBI animal model was established by controlled cortical impact (CCI). Cell apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL), and cell activity was detected by a cell counting kit 8 (CCK-8) assay. Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of related proteins and genes. In this study, transfection of miR-193b-3p into BMSCs significantly enhanced BMSCs proliferation and differentiation. Transfection of miR-193b-3p reduced the levels of the interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-alpha (TNF-α) inflammatory factors in cells and mouse models, and it inhibited neuronal apoptosis, which alleviated OGD-induced HT22 cell damage and neural function damage in TBI mice. Downstream experiments showed that miR-193b-3p targeting negatively regulated the expression of S1PR3, promoted the activation of the PI3K/AKT/mTOR signaling pathway, and inhibited the levels of apoptosis and inflammatory factors, which subsequently improved OGD-induced neuronal cell damage and nerve function damage in TBI mice. However, S1PR3 overexpression or inhibition of the PI3K/AKT/mTOR signaling pathway using the IN-2 inhibitor weakened the protective effect of miR-193b-3p-transfected BMSCs on HT22 cells. Transplantation of miR-193b-3p-transfected BMSCs inhibits neurological injury and improves the progression of TBI in mice through S1PR3-mediated regulation of the PI3K/AKT/mTOR pathway.
本研究旨在探讨经miR-193b-3p转染的骨髓间充质干细胞(BMSCs)移植改善创伤性脑损伤(TBI)后神经功能损伤的分子机制。1-磷酸鞘氨醇受体3(S1PR3)在细胞和动物水平上介导的磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶标(PI3K/AKT/mTOR)通路调节,改善创伤性脑损伤(TBI)后的神经损伤。用 miR-193b-3p 转染 BMSCs。通过氧-葡萄糖剥夺(OGD)诱导的 HT22 细胞建立了创伤性脑损伤细胞模型,通过可控皮质冲击(CCI)建立了创伤性脑损伤动物模型。细胞凋亡通过末端脱氧核苷酸转移酶(TdT)介导的 dUTP缺口末端标记(TUNEL)检测,细胞活性通过细胞计数试剂盒 8(CCK-8)检测。Western 印迹分析和定量实时聚合酶链反应(qRT-PCR)用于检测相关蛋白和基因的表达。在这项研究中,转染 miR-193b-3p 到 BMSCs 能显著增强 BMSCs 的增殖和分化。转染 miR-193b-3p 能降低细胞和小鼠模型中白细胞介素-6(IL-6)、IL-1β 和肿瘤坏死因子-α(TNF-α)等炎症因子的水平,抑制神经细胞凋亡,从而减轻 OGD 诱导的 HT22 细胞损伤和 TBI 小鼠的神经功能损伤。下游实验表明,miR-193b-3p靶向负调控S1PR3的表达,促进PI3K/AKT/mTOR信号通路的激活,抑制细胞凋亡和炎症因子的水平,从而改善OGD诱导的TBI小鼠神经细胞损伤和神经功能损伤。然而,S1PR3过表达或使用IN-2抑制剂抑制PI3K/AKT/mTOR信号通路会削弱miR-193b-3p转染BMSCs对HT22细胞的保护作用。通过 S1PR3 介导的 PI3K/AKT/mTOR 通路调节,移植 miR-193b-3p 转染的 BMSCs 可抑制神经损伤并改善小鼠创伤性脑损伤的进展。
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引用次数: 0
KRT6A inhibits IL-1β-mediated pyroptosis of keratinocytes via blocking IL-17 signaling KRT6A通过阻断IL-17信号传导抑制il -1β介导的角化细胞焦亡
IF 1.6 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-12-01 DOI: 10.1615/critreveukaryotgeneexpr.2023050039
Yuan Li, Qi Wu
Keratin 6A (KRT6A) is involved in the pathogenesis of various skin diseases. However, the reports on the roles of KRT6A in atopic dermatitis (AD) are limited. This study aimed to investigate the potentials of KRT6A in AD. mRNA levels were detected by RT-PCR. Cytokine release was determined by ELISA. Protein expression was determined using western blot. Cell viability was determined by CCK-8. Cytotoxicity was detected by LDH assay. Cell death was determined by TUNEL. The pyroptosis of keratinocytes was detected using flow cytometry. We found that KRT6A was overexpressed in AD patients. Moreover, KRT6A was stimulated after exposed to proinflammatory cytokines. Overexpressed KRT6A suppressed inflammatory response, while KRT6A knockdown exerted the opposite effects. Overexpressed KRT6A suppressed inflammation-induced pyroptosis of keratinocytes. Additionally, KRT6A negatively regulated IL-17A expression, blocking IL-17 signaling. IL-17a overexpression antagonized the effects of KRT6A and promoted pyroptosis of keratinocytes. In conclusion, KRT6A exerted protective functions in AD via regulating IL-17 signaling. This KRT6A/IL-17 may be a novel target for AD.
角蛋白6A (KRT6A)参与多种皮肤病的发病机制。然而,关于KRT6A在特应性皮炎(AD)中的作用的报道有限。本研究旨在探讨KRT6A在AD中的潜在作用。RT-PCR检测mRNA水平。ELISA法检测细胞因子释放量。western blot检测蛋白表达。CCK-8检测细胞活力。LDH法检测细胞毒性。TUNEL法测定细胞死亡情况。流式细胞术检测角质形成细胞的焦亡。我们发现KRT6A在AD患者中过表达。此外,KRT6A在暴露于促炎细胞因子后受到刺激。KRT6A过表达抑制炎症反应,而KRT6A敲低则发挥相反的作用。过表达KRT6A抑制炎症诱导的角化细胞焦亡。此外,KRT6A负调控IL-17A表达,阻断IL-17信号传导。IL-17a过表达可拮抗KRT6A的作用,促进角质形成细胞的焦亡。综上所述,KRT6A通过调节IL-17信号通路在AD中发挥保护作用。这个KRT6A/IL-17可能是AD的新靶点。
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引用次数: 0
Pathogens in Crohn’s Disease: the role of Adherent Invasive Escherichia Coli 克罗恩病的病原体:粘附性侵袭性大肠杆菌的作用
IF 1.6 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-12-01 DOI: 10.1615/critreveukaryotgeneexpr.2023050088
Gaetano Iaquinto, Vera Rotondi Aufiero, Giuseppe Mazzarella, Angela Lucariello, Luigi Panico, Raffaele Melina, Salvatore Iaquinto, Antonio De Luca, Carmine Sellitto
In Crohn’s disease (CD) gut dysbiosis is marked by the prevalence of pathogenic bacterial species. Although several microbes have been reported as risk factors or causative agents of CD, it is not yet clear which is the real trigger of the disease. Thirty years ago, a new pathovar of Escherichia Coli (E. coli) strain was isolated in the ileal mucosa of CD patients. This strain, called Adherent Invasive E. coli (AIEC), for its ability to invade the intestinal mucosa, could represent the causative agent of the disease. Several authors studied the mechanisms by which the AIEC penetrate and replicate within mac-rophages, and release inflammatory cytokines sustaining inflammation. In this review we will discuss about the role of AIEC in the pathogenesis of CD, the virulence factors mediating adhesion and invasion of AIEC in mucosal tissue, the environmental conditions improving AIEC survival and replication within macrophages. Finally, we will also give an overview of the new strategies developed to limit AIEC overgrowth.
在克罗恩病(CD)肠道失调的特点是流行的致病菌种类。虽然有几种微生物被报道为乳糜泻的危险因素或病原体,但尚不清楚哪一种是乳糜泻的真正诱因。30年前,在乳糜泻患者的回肠黏膜中分离到了一种新的病原菌大肠杆菌。这种菌株被称为附着性侵袭性大肠杆菌(AIEC),因为它能够侵入肠道粘膜,可能是这种疾病的病原体。几位作者研究了AIEC在巨噬细胞内渗透和复制,并释放炎症细胞因子维持炎症的机制。本文就AIEC在CD发病中的作用、介导AIEC在粘膜组织粘附和侵袭的毒力因子、促进AIEC在巨噬细胞内存活和复制的环境条件等方面进行综述。最后,我们还将概述为限制AIEC过度生长而制定的新策略。
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引用次数: 0
Identification of Potential Indicators for Survival in Patients with Thyroid Cancer Based on Expression of FAM3 Members. 基于FAM3成员表达的甲状腺癌患者生存的潜在指标鉴定
IF 1.6 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-01-01 DOI: 10.1615/CritRevEukaryotGeneExpr.2022044417
Yuting Ma, Junfeng Shi, Yongping Liu, Weiming Cui, Ruiyan Pan, Hongyan Qiu, Fang Han, Ningning Hou, Xiaodong Sun

Thyroid cancer (THCA) is a common head and neck malignancy. The family with sequence similarity 3 (FAM3) is a cytokine-like gene family with four members, which is presumed to participate in the development of many cancer types. However, the expression patterns of FAM3s in THCA and their prognostic values, have not yet been established. We investigated differential expressions of FAM3 mRNA and protein in THCA, then validated the findings for FAM3B by immunohistochemistry. We also investigated survival data with respect to FAM3 expression patterns in patients with THCA. FAM3s information regarding their relationships with clinical pathological parameters were obtained and FAM3 mutations were assessed. KEGG and GO pathway regarding FAM3C were obtained using online databases. To investigate potential correlations between FAM3s and immune cell infiltration, we investigated the roles of FAM3s in immune cells of patients with THCA. The mRNA expression of FAM3C were significantly elevated in THCA tissues; high expression levels of FAM3C protein were also observed in THCA tissues. A significant association between the pathological stage and the expression of FAM3C was found in patients with THCA. Patients with THCA who had high mRNA expression levels of FAM3C exhibited significantly more favorable prognosis, compared with patients who had low mRNA expression levels of FAM3C. Overall, FAM3C may play vital roles in the pathogenesis and development of THCA, and these findings constitute novel insights for biomarkers of immunotherapeutic targeted agents and may aid in the identification of prognostic biomarkers for THCA.

甲状腺癌(THCA)是常见的头颈部恶性肿瘤。FAM3家族(family with sequence similarity 3, FAM3)是一个有4个成员的细胞因子样基因家族,被认为参与了许多癌症类型的发展。然而,fam3在THCA中的表达模式及其预后价值尚未确定。我们研究了FAM3 mRNA和蛋白在THCA中的差异表达,并通过免疫组织化学验证了FAM3B的结果。我们还研究了THCA患者中FAM3表达模式的生存数据。获得FAM3s与临床病理参数的关系,并评估FAM3突变。利用在线数据库获得FAM3C的KEGG和GO通路。为了探讨FAM3s与免疫细胞浸润之间的潜在相关性,我们研究了FAM3s在THCA患者免疫细胞中的作用。FAM3C mRNA在THCA组织中的表达显著升高;FAM3C蛋白在THCA组织中也有高表达。THCA患者的病理分期与FAM3C的表达有显著相关性。FAM3C mRNA表达水平高的THCA患者预后明显好于FAM3C mRNA表达水平低的THCA患者。总之,FAM3C可能在THCA的发病和发展中发挥重要作用,这些发现为免疫治疗靶向药物的生物标志物提供了新的见解,并可能有助于确定THCA的预后生物标志物。
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引用次数: 0
MicroRNA-485-3p Promotes the Inflammatory Response and Extracellular Matrix Deposition by Activating Wnt/β-Catenin Signaling in Human Airway Smooth Muscle Cells. MicroRNA-485-3p通过激活人气道平滑肌细胞Wnt/β-Catenin信号通路促进炎症反应和细胞外基质沉积
IF 1.6 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-01-01 DOI: 10.1615/CritRevEukaryotGeneExpr.2022044300
Cuiyun Liu, Sen Shi, Ying Gao, Qian Leng, Rui Gong, Lan Zhang, Jinhai Ma

The aim of this study was to study the effects of microRNA (miR)-485-3p on the inflammatory response and extracellular matrix deposition of human airway smooth muscle cells (HASMCs). The levels of miR-485-3p and WIF1 in peripheral blood of pediatric asthma (PA) patients and controls were examined by quantitative real-time polymerase chain reaction (qRT-PCR). miR-485-3p inhibitor and mimic, together with negative control (NC) inhibitor/ mimic, were transfected into HASMCs treated with tumor necrosis factor (TNF)-α. The levels of eotaxin, interleukin (IL)-8, and IL-6 were analyzed by enzyme-linked immunosorbent assay (ELISA). Cellular immunofluorescence analysis of fibronectin was also performed. The target genes of miR-485-3p were predicted and validated using TargetScan and dual-luciferase reporter gene assay. The protein levels of IL-6, eotaxin, IL-8, collagen III, collagen I, MMP-9, TIMP-1, MMP-2, axin, β-catenin, phosphorylated β-catenin, GSK3β, p-GSK3β, and WIF1 were tested by Western blot. The level of miR-485-3p was increased, whereas expression of WIF1 was low in PA patients. In TNF-α-induced HASMCs, miR-485-3p overexpression promoted the inflammatory response and the accumulation of extracellular matrix. WIF1 was a direct target of miR-485-3p. Silencing miR-485-3p inhibited activation of Wnt/β-catenin signaling. The reductions in the inflammatory response and ECM accumulation caused by silencing miR-485-3p were induced by blocking Wnt/β-catenin signaling. Thus, miRNA-485-3p targets WIF1 and activates Wnt/β-catenin signaling, facilitating activation of the inflammatory response and ECM accumulation in HASMCs.

本研究旨在研究microRNA (miR)-485-3p对人气道平滑肌细胞(HASMCs)炎症反应和细胞外基质沉积的影响。采用实时定量聚合酶链式反应(qRT-PCR)检测小儿哮喘(PA)患者和对照组外周血中miR-485-3p和WIF1的水平。将miR-485-3p抑制剂和模拟物以及阴性对照(NC)抑制剂/模拟物转染到经肿瘤坏死因子(TNF)-α处理的HASMCs中。采用酶联免疫吸附试验(ELISA)分析eotaxin、白细胞介素(IL)-8、IL-6水平。同时进行纤维连接蛋白的细胞免疫荧光分析。采用TargetScan和双荧光素酶报告基因法预测和验证miR-485-3p的靶基因。Western blot检测IL-6、eotaxin、IL-8、collagen III、collagen I、MMP-9、TIMP-1、MMP-2、axin、β-catenin、磷酸化β-catenin、GSK3β、p-GSK3β、WIF1蛋白水平。PA患者miR-485-3p水平升高,而WIF1表达较低。在TNF-α-诱导的HASMCs中,miR-485-3p过表达促进了炎症反应和细胞外基质的积累。WIF1是miR-485-3p的直接靶点。沉默miR-485-3p可抑制Wnt/β-catenin信号通路的激活。沉默miR-485-3p引起的炎症反应和ECM积累的减少是通过阻断Wnt/β-catenin信号传导诱导的。因此,miRNA-485-3p靶向WIF1并激活Wnt/β-catenin信号,促进炎症反应的激活和HASMCs中ECM的积累。
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引用次数: 0
The Function and Mechanism of Long Non-Coding RNA RP11-23J9.4 in Thyroid Cancer. 长链非编码RNA RP11-23J9.4在甲状腺癌中的作用及机制
IF 1.6 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-01-01 DOI: 10.1615/CritRevEukaryotGeneExpr.2022046595
Lili Zhong, Xiangfu Ding, Xiaoliang Xiong, Tingting Hao, Chao Zhang, Lixing Wang, Yinlong Zhao

Introduction: The objective of this research is to explore whether LncRNA RP11 23J9.4 can be used as a targeted marker for the treatment of thyroid cancer (TC), downregulation of LncRNA RP11 23J9.4 and X-ray radiation have synergistic inhibitory effect on TC.

Methods: The expression of LncRNA RP11 23J9.4 in papillary thyroid carcinoma (PTC) cell was downregulated by cell transfection, and its inhibitory effect on PTC cells was proved through proliferation, invasion experiment, apoptosis, and cell cycle analysis. The transfected cells were irradiated with 2 Gy X-ray. The above methods were also used to detect whether they had synergistic inhibitory effect on TC. The expression of Axin2 gene and protein were detected by real-time PCR, Western blotting, and immunohistochemistry.

Results: On the one hand, it is proved that downregulating the expression of LncRNA RP11 23J9.4 can inhibit the development of TC through Axin2. On the other hand, it is clear that downregulation of LncRNA RP11 23J9.4 and X-ray radiation have synergistic inhibitory effect on TC.

Conclusions: LncRNA RP11 23J9.4 and X-ray have significant synergistic effect on TC. LncRNA RP11 23J9.4 can be used as a marker for TC targeted therapy.

简介:本研究旨在探讨LncRNA RP11 23J9.4是否可以作为治疗甲状腺癌(TC)的靶向标志物,LncRNA RP11 23J9.4下调与x射线辐射对TC有协同抑制作用。方法:通过细胞转染下调LncRNA RP11 23J9.4在甲状腺乳头状癌(PTC)细胞中的表达,并通过增殖、侵袭实验、细胞凋亡和细胞周期分析证实其对PTC细胞的抑制作用。转染后的细胞用2gy x射线照射。并采用上述方法检测其对TC是否具有协同抑制作用。采用实时荧光定量PCR、Western blotting、免疫组化检测Axin2基因及蛋白的表达。结果:一方面证明下调LncRNA RP11 23J9.4的表达可通过Axin2抑制TC的发生。另一方面,LncRNA RP11 23J9.4下调与x射线辐射对TC有协同抑制作用。结论:LncRNA RP11 23J9.4与x射线对TC有显著的协同作用。LncRNA RP11 23J9.4可作为TC靶向治疗的标志物。
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引用次数: 0
UTP23 is a prominsing prognostic biomarker and is associated with immune infiltration in breast cancer UTP23是一个重要的预后生物标志物,与乳腺癌的免疫浸润有关
4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-01-01 DOI: 10.1615/critreveukaryotgeneexpr.2023048311
Jindong Li, Siman Xie, Benteng Zhang, Weiping He, Yan Zhang, Jun Wang, Li Yang
Background: Breast cancer is one of the malignant tumors with a high incidence and mortality rate among women worldwide, and its prevalence is increasing year by year, posing a serious health risk to women. UTP23 (UTP23 Small Subunit Processome Component) is a nucleolar protein that is essential for ribosome production. As we all know, disruption of ribosome structure and function results in improper protein function, affecting the body's normal physiological processes and promoting cancer growth. However, little research has shown a connection between UTP23 and cancer. Methods: We analyzed the mRNA expression of UTP23 in normal tissue and breast cancer using The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, and the protein expression of UTP23 using The Human Protein Atlas (HPA) database. Next, we examined the relationship between UTP23 high expression and Overall Survival (OS) using Kaplan-Meier Plotters and enriched 980 differentially expressed genes in UTP23 high and low expression samples using GO/KEGG and GSEA to identify potential biological functions of UTP23 and signaling pathways that it might influence. Finally, we also investigated the relationship between UTP23 and immune infiltration and examined the effect of UTP23 on the proliferation of human breast cancer cell lines by knocking down UTP23. Results: We found that UTP23 levels in breast cancer patient samples were noticeably greater than those in healthy individuals and that high UTP23 levels were strongly linked with poor prognoses (P=0.008). Functional enrichment analysis revealed that UTP23 expression was connected to the humoral immune response. Besides, UTP23 expres
背景:乳腺癌是世界范围内妇女发病率高、死亡率高的恶性肿瘤之一,其发病率呈逐年上升趋势,对妇女健康构成严重威胁。UTP23 (UTP23小亚单位加工成分)是核糖体产生所必需的核核蛋白。众所周知,核糖体结构和功能的破坏导致蛋白质功能不正常,影响机体的正常生理过程,促进肿瘤生长。然而,很少有研究表明UTP23与癌症之间存在联系。方法:利用cancer Genome Atlas (TCGA)数据库和Gene expression Omnibus (GEO)数据库分析正常组织和乳腺癌中UTP23 mRNA的表达,利用Human protein Atlas (HPA)数据库分析UTP23蛋白的表达。接下来,我们利用Kaplan-Meier绘图仪检测了UTP23高表达与总生存率(OS)之间的关系,并利用GO/KEGG和GSEA富集了UTP23高表达和低表达样本中的980个差异表达基因,以确定UTP23的潜在生物学功能及其可能影响的信号通路。最后,我们还研究了UTP23与免疫浸润的关系,并通过敲低UTP23检测了UTP23对人乳腺癌细胞系增殖的影响。结果:我们发现乳腺癌患者样本中的UTP23水平明显高于健康个体,并且UTP23水平高与预后不良密切相关(P=0.008)。功能富集分析显示,UTP23的表达与体液免疫应答有关。此外,UTP23表达
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引用次数: 0
DLEU2/EZH2/GFI1 axis regulates the proliferation and apoptosis of hBMSCs DLEU2/EZH2/GFI1轴调控hBMSCs的增殖和凋亡
4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-01-01 DOI: 10.1615/critreveukaryotgeneexpr.2023050337
Qing Yao, Xuezhi He, Jing Wang, Juan Liu, Qing Zhang, Jie Zhang, Yawen Bo, Lin Lu
Long non-coding RNAs (lncRNAs) has become a vital regulator in the pathogenesis of osteoporosis (OP). This study aimed to investigate the role of lncRNA DLEU2 in the development of proliferation and apoptosis of hBMSCs. High-throughput sequencing in bone tissues from 3 pairs healthy donors and OP patients was used to search for differential lncRNAs. The expression of DLEU2 was also verified in bone tissues. The hBMSCs were transfected with DLEU2 ASO. Cell viability was detected suing MTT. Cell proliferation was determined using colony formation and EdU assays. Cell cycle and apoptosis was detected using flow cytometry. RIP, RNA pulldown, and Co-IP assays were carried out to verify the interaction between protein and protein/RNA. The binding sites between GFI1 and the promoter of DLEU2 was verified using ChIP and luciferase assays. DLEU2 expression was down-regulated in OP patients. Knockdown of DLEU2 expression significantly inhibited proliferation and promoted apoptosis of hBMSCs via up-regulating the expression of Bax and Caspase3. Moreover, DLEU2 could interact with EZH2 to induce the activation of GFI1. Additionally, GFI1 transcriptionally activated DLEU2. Taken together, DLEU2/EZH2/GFI1 axis suppressed proliferation and enhanced hBMSC apoptosis. This may provide novel strategy for OP.
长链非编码rna (lncRNAs)已成为骨质疏松症(OP)发病机制中的重要调控因子。本研究旨在探讨lncRNA DLEU2在hBMSCs增殖和凋亡过程中的作用。对3对健康供体和OP患者的骨组织进行高通量测序,以寻找差异lncrna。在骨组织中也证实了DLEU2的表达。用DLEU2 ASO转染hBMSCs。用MTT检测细胞活力。用菌落形成和EdU测定细胞增殖。流式细胞术检测细胞周期和凋亡。采用RIP、RNA pull - down和Co-IP实验验证蛋白与蛋白/RNA之间的相互作用。GFI1与DLEU2启动子之间的结合位点通过ChIP和荧光素酶测定验证。在OP患者中,DLEU2表达下调。敲低DLEU2表达可通过上调Bax和Caspase3的表达,显著抑制hBMSCs的增殖,促进细胞凋亡。此外,DLEU2可以与EZH2相互作用,诱导GFI1的激活。此外,GFI1转录激活了DLEU2。综上所述,dele2 /EZH2/GFI1轴抑制hBMSC增殖,增强hBMSC凋亡。这可能为OP提供新的策略。
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引用次数: 0
Pan-cancer analysis of the LOX family reveals that LOX affects tumor prognosis by affecting immune infiltration LOX家族的泛癌分析表明,LOX通过影响免疫浸润影响肿瘤预后
4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-01-01 DOI: 10.1615/critreveukaryotgeneexpr.2023049049
Chunlong Zheng, Nian Zhang, Yan Chu, Ting Jia, Yuanyuan Li, Jiang Tao, Jianyong Sun
Background: The LOX (lysyl oxidase) gene family encodes for a group of copper-dependent enzymes that play a crucial role in the cross-linking of collagen and elastin fibers in the extracellular matrix (ECM). Dysregulation of LOX gene expression has been implicated in various pathological conditions, including cancer. Objectives: The goal of this article is to conduct a comprehensive analysis of the LOX family's role in pan-cancer multiplexes. Material and methods: We utilized pan-cancer multi-omics sequencing data from TCGA to investigate the relationship between LOX family genes and tumors at four different levels: mutation, copy number variation, methylation, and gene expression. In addition, we also examined the relationship between LOX family genes and tumors at the cell line level using tumor cell line sequencing data from CCLE. Results: Our findings revealed that LOXL2 had the highest mutation frequency in tumors, while all four LOX family genes experienced some degree of copy number variation in diverse tumors. We observed that LOX, LOXL1-3 were predominantly highly expressed in tumors including LUAD. The expression trends of LOX and LOXL1-3 were consistent across tumor cell lines, but differed somewhat from LOXL4. Utilizing 25 LOX family-related genes, we constructed a LOX family prognostic model that performed well in predicting the prognosis of lung cancer. Conclusions: Through pan-cancer analysis, we gain further knowledge of the role of LOX family genes in different tumors, offering a novel pathway for future research into the relationship between LOX family genes and tumors.
背景:赖氨酸氧化酶(LOX)基因家族编码一组铜依赖性酶,这些酶在细胞外基质(ECM)中胶原和弹性蛋白纤维的交联中起关键作用。LOX基因表达的失调与包括癌症在内的各种病理状况有关。目的:本文的目的是全面分析LOX家族在泛癌症多重因素中的作用。材料和方法:利用TCGA的泛肿瘤多组学测序数据,从突变、拷贝数变异、甲基化和基因表达四个不同水平研究LOX家族基因与肿瘤的关系。此外,我们还利用CCLE的肿瘤细胞系测序数据,在细胞系水平上研究了LOX家族基因与肿瘤之间的关系。结果:我们的研究结果显示LOXL2在肿瘤中的突变频率最高,而LOX家族的四个基因在不同的肿瘤中都有一定程度的拷贝数变异。我们观察到LOX、LOXL1-3在包括LUAD在内的肿瘤中主要高表达。LOX和LOXL1-3在不同肿瘤细胞系的表达趋势一致,但与LOXL4有一定差异。利用25个LOX家族相关基因,我们构建了LOX家族预后模型,该模型在预测肺癌预后方面表现良好。结论:通过泛癌分析,我们进一步了解了LOX家族基因在不同肿瘤中的作用,为进一步研究LOX家族基因与肿瘤的关系提供了新的途径。
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Critical Reviews in Eukaryotic Gene Expression
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