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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 Biochemistry, Genetics and Molecular Biology 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 Biochemistry, Genetics and Molecular Biology 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 Biochemistry, Genetics and Molecular Biology 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
BAG2 Is a Novel Prognostic Biomarker and Promising Immunotherapy Target in Uveal Melanoma. BAG2是一种新的预后生物标志物和有希望的葡萄膜黑色素瘤免疫治疗靶点。
IF 1.6 4区 医学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.1615/CritRevEukaryotGeneExpr.2023048565
Chaolin Li, Hao Shi

Background: The importance of BAG2 in malignancy is gradually being recognized, however, information on its role in uveal melanoma (UVM) is limited. We aimed to elucidate its function and potential mechanism of action in UVM.

Methods: Using the Cancer Genome Atlas (TCGA) and GEO-related datasets, we analyzed the differential expression of BAG2 in tumors, combined with clinical information and methylation data to analyze the prognostic value of BAG2, differential methylation and its association with UVM metastasis. In addition, correlation analysis explored the immunological characteristics of BAG2 in UVM and the response to immunotherapy. Finally, a prognostic model of ferroptosis- related genes was constructed and validated.

Results: BAG2 is significantly downregulated in multiple cancers including UVM. Prognostic analysis showed that BAG2 was an independent prognostic factor for UVM. Abnormal methylation of BAG2 may affect the metastasis of UVM and be significantly associated with poor prognosis. Immune analysis clarified that BAG2 was significantly associated with UVM immune cell infiltration and multiple immune checkpoints, and low expression of BAG2 was more beneficial in immunotherapy. In addition, the prognostic model of ferroptosis we constructed has good performance in predicting overall survival and metastasis-free survival of UVM.

Conclusions: BAG2 is an independent prognostic factor for UVM and may be a potential immune checkpoint for UVM.

背景:BAG2在恶性肿瘤中的重要性正逐渐被认识到,然而,关于其在葡萄膜黑色素瘤(UVM)中的作用的信息有限。我们旨在阐明其在UVM中的作用及其潜在机制。方法:利用肿瘤基因组图谱(Cancer Genome Atlas, TCGA)和geo相关数据集,分析BAG2在肿瘤中的差异表达,结合临床信息和甲基化数据,分析BAG2的预后价值、差异甲基化及其与UVM转移的关系。此外,通过相关分析探讨了BAG2在UVM中的免疫学特性及其对免疫治疗的反应。最后,构建并验证了铁下垂相关基因的预后模型。结果:BAG2在包括UVM在内的多种癌症中显著下调。预后分析显示BAG2是UVM的独立预后因素。BAG2异常甲基化可能影响UVM的转移,并与不良预后显著相关。免疫分析表明BAG2与UVM免疫细胞浸润和多个免疫检查点显著相关,低表达BAG2在免疫治疗中更有利。此外,我们构建的铁下垂预后模型在预测UVM的总生存期和无转移生存期方面具有良好的性能。结论:BAG2是UVM的独立预后因素,可能是UVM的潜在免疫检查点。
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引用次数: 0
Long Non-Coding RNA LPP-AS2 Plays an Anti-Tumor Role in Thyroid Carcinoma by Regulating the miR-132-3p/OLFM1 Axis. 长非编码 RNA LPP-AS2 通过调控 miR-132-3p/OLFM1 轴在甲状腺癌中发挥抗肿瘤作用
IF 1.6 4区 医学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.1615/CritRevEukaryotGeneExpr.v33.i5.70
Bowei Zhang, Tong Liu, Yi Gu, Li Ren, Jinju Wang, Chao Feng, Zhe Song

The cancer-promoting function of the long non-coding RNA (lncRNA) LPP-AS2 has been documented in different cancers. Nonetheless, its role in thyroid carcinoma (THCA) remains unestablished. Reverse transcription quantitative polymerase chain reaction and Western blotting were conducted to estimate the expressions of lncRNA LPP-AS2, miR-132-3p, and OLFM1. The THCA cells' functions were assessed through CCK8 assays, Transwell invasion assays, scratch wound-healing migration assays, and quantification of caspase-3 activity. The in vivo assays were also implemented to assess tumor growth. Luciferase reporter and RNA immuno-precipitation assay (RIPA) experiments were executed to elucidate the interactions of miR-132-3p with lncRNA LPP-AS2 and OLFM1. THCA tissues and cells exhibited poor lncRNA LPP-AS2 and OLFM1 expressions and a robust expression of miR-132-3p. Overexpressing lncRNA LPP-AS2 constrained THCA cell proliferation, migration, and invasion and improved caspase-3 activity. The anti-tumor function of lncRNA LPP-AS2 was also validated in vivo. miR-132-3p had an interplay with lncRNA LPP-AS2 and OLFM1. Functionally, overexpressing miR-132-3p promoted the malignant THCA cell phenotypes. However, that tumor promotion was abolished by the additional overexpression of lncRNA LPP-AS2. The in vitro experiments also demonstrated that the repressive effect of OLFM1 overexpression on THCA cell malignant action could be offset by the miR-132-3p mimic. lncRNA LPP-AS2 impedes THCA progression via the miR-132-3p/OLFM1 axis. Our findings contribute a potential strategy in interfering with THCA progression.

长非编码 RNA(lncRNA)LPP-AS2 在不同癌症中的促癌功能已被证实。然而,它在甲状腺癌(THCA)中的作用仍未确定。研究人员通过逆转录定量聚合酶链反应和 Western 印迹法估测了 lncRNA LPP-AS2、miR-132-3p 和 OLFM1 的表达。通过CCK8检测、Transwell侵袭检测、划痕伤口愈合迁移检测和caspase-3活性定量来评估THCA细胞的功能。体内试验也用于评估肿瘤生长。为了阐明 miR-132-3p 与 lncRNA LPP-AS2 和 OLFM1 的相互作用,还进行了荧光素酶报告实验和 RNA 免疫沉淀实验(RIPA)。THCA组织和细胞的lncRNA LPP-AS2和OLFM1表达较差,而miR-132-3p表达强劲。过表达lncRNA LPP-AS2会抑制THCA细胞的增殖、迁移和侵袭,并改善caspase-3的活性。miR-132-3p 与 lncRNA LPP-AS2 和 OLFM1 之间存在相互作用。从功能上讲,过表达 miR-132-3p 会促进 THCA 细胞的恶性表型。然而,额外的lncRNA LPP-AS2过表达则会消除这种肿瘤促进作用。体外实验还表明,OLFM1过表达对THCA细胞恶性作用的抑制作用可被miR-132-3p模拟物抵消。lncRNA LPP-AS2通过miR-132-3p/OLFM1轴阻碍THCA进展。我们的发现为干扰THCA的进展提供了一种潜在的策略。
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引用次数: 0
IncRNA MALAT1 Regulates the Proliferation, Apoptosis, Migration, and Invasion of Osteosarcoma Cells by Targeting miR-873-5p/ROCK1. IncRNA MALAT1通过靶向miR-873-5p/ROCK1调控骨肉瘤细胞的增殖、凋亡、迁移和侵袭
IF 1.6 4区 医学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.1615/CritRevEukaryotGeneExpr.2022044747
Fan Yang, Mao Wang, Junlong Shi, Gang Xu

The malignant bone tumor osteosarcoma (OS) was one of the most aggressive tumors. Despite breakthroughs in treatment options for OS recently, the survival rate of patients with metastasis or reoccurring disease has remained unchanged over the last 25 years, at around 20%. lncRNA expression dysregulation is linked to carcinogenesis, advancement, and metastasis. Additionally, the fundamental mechanism of lncRNAs in regulating OS cell biological activity and progression is still being investigated. The expression of miR-873-5p and MALAT1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in OS. The relationship between the expression level of MALAT1 and the survival rate of OS individuals was evaluated by the Kaplan-Meier plotter. The tumor cell's capability of proliferation was determined using the CCK-8. Transwell was used to test the migratory and invasive properties of tumor cells. ROCK1 protein expression was analyzed by western blot, while qRT-PCR was used to detect ROCK1 mRNA expression. Targeted genes of MALAT1 or miR-873-5p were predicted by StarBase2.0. The target association among miR-873-5p and MALAT1 or ROCK1 was confirmed using the luciferase assay. The relationship between ROCK1 and MALAT1 or miR-873-5p expression in OS was investigated using Spearman's correlation analysis. MALAT1 was up-regulated and was linked to a lower survival rate of patients in OS. The malignant behaviors of cells were inhibited by down-regulated MALAT1 in vitro. Dual-luciferase gene experiments confirmed the presence of MALAT1/miR-873-5p/ROCK1 axis. The up-regulated miR-873-5p blocked the promoted effects of MALAT1 on cell behaviors. Over-expressed MALAT1 promoted the malignant behaviors of cells by miR-873-5p/ROCK1 axis in OS.

骨恶性肿瘤骨肉瘤(osteosarcoma, OS)是最具侵袭性的肿瘤之一。尽管最近在OS的治疗选择上取得了突破,但在过去的25年里,转移或复发疾病患者的生存率保持不变,约为20%。lncRNA表达失调与癌症发生、进展和转移有关。此外,lncRNAs调控OS细胞生物活性和进展的基本机制仍在研究中。采用实时定量聚合酶链反应(qRT-PCR)检测OS中miR-873-5p和MALAT1的表达。通过Kaplan-Meier绘图仪评估MALAT1表达水平与OS个体生存率的关系。采用CCK-8检测肿瘤细胞的增殖能力。Transwell用于检测肿瘤细胞的迁移和侵袭特性。western blot检测ROCK1蛋白表达,qRT-PCR检测ROCK1 mRNA表达。利用StarBase2.0预测MALAT1或miR-873-5p的靶基因。通过荧光素酶测定证实miR-873-5p与MALAT1或ROCK1之间的靶标关联。采用Spearman相关分析研究ROCK1与OS中MALAT1或miR-873-5p表达的关系。MALAT1表达上调,与OS患者较低的生存率有关。下调MALAT1可抑制细胞的恶性行为。双荧光素酶基因实验证实存在MALAT1/miR-873-5p/ROCK1轴。上调的miR-873-5p阻断了MALAT1对细胞行为的促进作用。过表达MALAT1可通过miR-873-5p/ROCK1轴促进OS细胞的恶性行为。
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引用次数: 3
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 Biochemistry, Genetics and Molecular Biology 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 Biochemistry, Genetics and Molecular Biology 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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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 Biochemistry, Genetics and Molecular Biology 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
Raising the HPV Vaccination Rate in Rural Northern New England Using Local Opinion Leaders. 利用当地意见领袖提高新英格兰北部农村HPV疫苗接种率。
IF 1.6 4区 医学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.1615/CritRevEukaryotGeneExpr.2023048915
Matthew Dugan, Gary S Stein, Shamima Khan, Sheila Clifford-Bova Clifford-Bova, Finlay Pilcher, Jan Kirk Carney

The human papillomavirus is associated with a range of cancers. A vaccine introduced in 2006 has dramatically decreased the incidence of these cancers, but Americans still experience over 47,000 new cases of HPV-related cancers each year. The situation is worse in rural areas, where vaccination rates lag the national average, making HPV a significant health disparity issue. This article lays out an evidence-based HPV vaccine-promotion strategy that will serve as part of a campaign to improve health equity in rural northern New England in a process that is repeatable and sustainable. The campaign includes the following elements: partnerships with state departments of health and trusted community opinion leaders, evidence-based storytelling, local social media, traditional media, and school-based pop-up vaccination clinics. Borrowing from marketing and social marketing frameworks and guided by public health perspectives, we begin with psychographic and geodemographic information about our target audience, followed by a discussion about relevant models, frameworks, and research related to persuasive storytelling. We conclude with the outline of a guidebook to foster the creation of persuasive stories as part of a sustainable, replicable HPV vaccination campaign.

人类乳头瘤病毒与一系列癌症有关。2006年推出的一种疫苗大大降低了这些癌症的发病率,但美国人每年仍有超过47,000例hpv相关癌症的新病例。农村地区的情况更糟,那里的疫苗接种率落后于全国平均水平,使HPV成为一个重大的健康差距问题。本文提出了一项基于证据的HPV疫苗推广策略,该策略将作为一项运动的一部分,在可重复和可持续的过程中改善新英格兰北部农村的卫生公平。该运动包括以下要素:与州卫生部门和值得信赖的社区意见领袖建立伙伴关系,以证据为基础讲故事,当地社交媒体,传统媒体和以学校为基础的弹出式疫苗接种诊所。借鉴市场营销和社会营销框架,并以公共卫生观点为指导,我们从目标受众的心理和地理人口统计信息开始,然后讨论有关有说服力的故事讲述的相关模型、框架和研究。最后,我们概述了一本指导手册,以促进有说服力的故事的创作,作为可持续的、可复制的HPV疫苗接种运动的一部分。
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引用次数: 0
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Critical Reviews in Eukaryotic Gene Expression
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