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Transcriptome Classification Reveals Molecular Subgroups in Idiopathic Pulmonary Fibrosis. 转录组分类揭示特发性肺纤维化的分子亚群。
IF 1.5 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2022-07-16 eCollection Date: 2022-01-01 DOI: 10.1155/2022/7448481
Yuxia Liu, Chang Xu, Wenxin Gao, Huaqiong Liu, Chenglong Li, Mingwei Chen

Idiopathic pulmonary fibrosis (IPF) is a disease of progressive lung fibrosis with a high mortality rate. This study aimed to uncover the underlying molecular features for different types of IPF. IPF microarray datasets were retrieved from GEO databases. Weighted gene co-expression analysis (WGCNA) was used and identified subgroup-specific WGCNA modules. Infiltration-level immune cells in different subgroups of microenvironments were analyzed with CIBERSORT algorithms. The result is we classified 173 IPF cases into two subgroups based on gene expression profiles, which were retrieved from the GEO databases. The SGRQ score and age were significantly higher in C2 than in C1. Using WGCNA, five subgroup-specific modules were identified. M4 was mainly enriched by MAPK signaling, which was mainly expressed in C2; M1, M2, and M3 were mainly enriched by metabolic pathways and Chemokine signaling, and the pathway of M5 was phagosome inflammation; M1, M2, M3, and M5 were mainly expressed in C1. Utilizing the CIBERSORT, we showed that the number of M1 macrophage cells, CD8 T cells, regulatory T cells (Tregs), and Plasma cells was significantly different between C1 and C2. We found the molecular subgroups of IPF revealed that cases from different subgroups may have their unique patterns and provide novel information to understand the mechanisms of IPF itself.

特发性肺纤维化(IPF)是一种死亡率高的进行性肺纤维化疾病。本研究旨在揭示不同类型IPF的潜在分子特征。IPF微阵列数据集从GEO数据库检索。采用加权基因共表达分析(加权基因共表达分析,WGCNA)鉴定亚群特异性WGCNA模块。采用CIBERSORT算法对不同微环境亚群的浸润水平免疫细胞进行分析。结果是,我们根据从GEO数据库中检索到的基因表达谱将173例IPF病例分为两个亚组。C2组SGRQ评分及年龄明显高于C1组。使用WGCNA,确定了五个特定于亚组的模块。M4主要富集MAPK信号,主要表达于C2;M1、M2、M3主要通过代谢途径和趋化因子信号通路富集,M5途径为吞噬体炎症;M1、M2、M3、M5主要在C1表达。利用CIBERSORT,我们发现M1巨噬细胞、CD8 T细胞、调节性T细胞(Tregs)和浆细胞的数量在C1和C2之间存在显著差异。我们发现IPF的分子亚群揭示了不同亚群的病例可能有其独特的模式,为理解IPF本身的机制提供了新的信息。
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引用次数: 0
Association of the Interleukin-10-592C/A Polymorphism and Cervical Cancer Risk: A Meta-Analysis. 白细胞介素-10-592C/A 多态性与宫颈癌风险的关系:一项 Meta 分析。
IF 1.4 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2022-07-12 eCollection Date: 2022-01-01 DOI: 10.1155/2022/2319161
Brehima Diakite, Yaya Kassogue, Mamoudou Maiga, Guimogo Dolo, Oumar Kassogue, Jonah Musa, Imran Morhason-Bello, Ban Traore, Cheick Bougadari Traore, Bakarou Kamate, Aissata Coulibaly, Sekou Bah, Sellama Nadifi, Robert Murphy, Jane L Holl, Lifang Hou

A literature review showed some discrepancies regarding the association of -592C/A with the risk of cervical cancer. To allow more precise analysis of the data by increasing the number of cases studied and more acceptable generalization by considering results from different sources, the present meta-analysis was performed on available published studies that explored the relationship between SNP-592C/A of the IL-10 gene and the risk of cervical cancer. Eleven available studies, including 4187 cases and 3311 controls, were included in this study investigating the relationship between the -592C/A polymorphism of IL-10 and cervical cancer risk. Fixed-effects or random-effects models were performed with pooled odds ratios (ORs). Heterogeneity and bias tests were performed by the inconsistency test and funnel plot, respectively. The overall analysis showed an increased susceptibility to cervical cancer with the -592C/A polymorphism of the IL-10 gene for the recessive model (OR = 1.30, 95% CI = 1.14-1.49), dominant model (OR = 1.36, 95% CI = 1.09-1.70), and additive model (OR = 1.25, 95% CI = 1.09-1.44). Regarding ethnicity, a significant association of the -592C/A polymorphism of the IL-10 gene was linked to an elevated risk of cervical cancer for all genetic models (recessive, dominant, and additive) in the Asian populations and for the recessive and additive models in Caucasians with P < 0.05. The -592C/A polymorphism of the IL-10 gene may be considered a risk factor for cervical cancer.

文献综述显示,-592C/A 与宫颈癌风险的关系存在一些差异。为了通过增加研究病例的数量来对数据进行更精确的分析,并通过考虑不同来源的结果来进行更容易接受的归纳,本荟萃分析对已发表的探讨 IL-10 基因 SNP-592C/A 与宫颈癌风险之间关系的现有研究进行了分析。本研究共纳入了 11 项现有研究,包括 4187 例病例和 3311 例对照,这些研究均探讨了 IL-10 基因-592C/A 多态性与宫颈癌风险之间的关系。研究采用固定效应或随机效应模型,并汇总了几率比(ORs)。异质性和偏倚检验分别通过不一致性检验和漏斗图进行。总体分析结果显示,IL-10基因的-592C/A多态性在隐性模型(OR=1.30,95% CI=1.14-1.49)、显性模型(OR=1.36,95% CI=1.09-1.70)和加性模型(OR=1.25,95% CI=1.09-1.44)中均增加了宫颈癌的易感性。在种族方面,IL-10基因的-592C/A多态性与宫颈癌风险的升高有显著关联,在亚洲人群中的所有遗传模型(隐性、显性和加性)以及在白种人中的隐性和加性模型中,P<0.05。IL-10基因的-592C/A多态性可被视为宫颈癌的风险因素。
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引用次数: 0
Hsa-let-7c-5p, hsa-miR-130b-3p, and hsa-miR-142-3p as Novel miRNA Biomarkers for Melanoma Progression. Hsa-let-7c-5p, hsa-miR-130b-3p和hsa-miR-142-3p作为黑色素瘤进展的新型miRNA生物标志物
IF 2.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2022-07-07 eCollection Date: 2022-01-01 DOI: 10.1155/2022/5671562
Xuerui Wu, Yu Wang, Chen Chen, Yadong Xue, Shuyun Zheng, Limin Cai

This study aimed to screen miRNA biomarkers for melanoma progression. Raw melanoma data were downloaded from the Gene Expression Omnibus (GSE34460, GSE35579, GSE18509, and GSE24996) and the Cancer Genome Atlas (TCGA). Then, all differentially expressed miRNAs (DEmiRNAs) between benign vs. primary, metastatic vs. benign, and metastatic vs. primary groups were obtained in the GSE34460 and GSE35579 datasets, and the miRNAs related to disease progression were further screened. Then, the miRNA-gene network was constructed, followed by enrichment, survival, and cluster analyses. Differentially expressed genes (DEGs), tumor-infiltrating immune cells, and tumor mutation burden (TMB) between subtypes were analyzed. miRNAs were verified in the GSE18509 and GSE24996 datasets. A total of 132 and 209 DEmiRNAs were obtained in the GSE34460 and GSE35579 datasets, respectively, and 27 DEmiRNAs related to disease progression were screened. hsa-miR-106b-5p, hsa-miR-27b-3p, and hsa-miR-141-3p had a higher degree and were regulated by numerous genes in the miRNA-gene network. Moreover, four miRNAs were associated with prognosis: hsa-let-7c-5p, hsa-miR-130b-3p, hsa-miR-142-3p, and hsa-miR-509-3p. Furthermore, the bidirectional hierarchical clustering of 27 miRNAs was classified into three subtypes, and TMB and four types of immune cells, including activated dendritic cells, naïve CD4 T cells, M1 macrophages, and plasma cells, showed significant differences among the three subtypes. The expression levels of most miRNAs in the GSE18509 and GSE24996 datasets were consistent with those in the training dataset. These miRNAs, including hsa-let-7c-5p, hsa-miR-130b-3p, and hsa-miR-142-3p, and activated dendritic cells, naïve CD4 T cells, M1 macrophages, and plasma cells may play vital roles in the pathogenesis of melanoma.

本研究旨在筛选黑色素瘤进展的miRNA生物标志物。原始黑色素瘤数据从基因表达Omnibus (GSE34460、GSE35579、GSE18509和GSE24996)和癌症基因组图谱(TCGA)下载。然后,在GSE34460和GSE35579数据集中获得良性组与原发性组、转移性组与良性组、转移性组与原发性组之间的所有差异表达miRNAs (DEmiRNAs),并进一步筛选与疾病进展相关的miRNAs。然后,构建mirna基因网络,随后进行富集、存活和聚类分析。分析不同亚型之间的差异表达基因(DEGs)、肿瘤浸润免疫细胞和肿瘤突变负荷(TMB)。在GSE18509和GSE24996数据集中验证了mirna。在GSE34460和GSE35579数据集中分别获得了132和209个demirna,并筛选了27个与疾病进展相关的demirna。hsa-miR-106b-5p、hsa-miR-27b-3p和hsa-miR-141-3p的表达程度较高,受mirna基因网络中众多基因的调控。此外,四种mirna与预后相关:hsa-let-7c-5p、hsa-miR-130b-3p、hsa-miR-142-3p和hsa-miR-509-3p。此外,27个mirna的双向分层聚类被划分为3个亚型,TMB与活化树突状细胞、naïve CD4 T细胞、M1巨噬细胞、浆细胞等4种免疫细胞在3个亚型之间存在显著差异。GSE18509和GSE24996数据集中大多数mirna的表达水平与训练数据集中一致。这些mirna包括hsa-let-7c-5p、hsa-miR-130b-3p和hsa-miR-142-3p,以及活化的树突状细胞、naïve CD4 T细胞、M1巨噬细胞和浆细胞可能在黑色素瘤的发病过程中发挥重要作用。
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引用次数: 0
Bioinformatics Analysis of Exercise-Related Biomarkers in Diabetes. 糖尿病运动相关生物标志物的生物信息学分析。
IF 1.5 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2022-06-29 eCollection Date: 2022-01-01 DOI: 10.1155/2022/1273153
Xiaoju Bao, Jingyue Qiu, Qin Xuan, Xinming Ye

Background: Exercise is a regular behavioral activity that not only helps to lose weight but also reduces the risk of cardiovascular and cerebrovascular diseases. Diabetes is a common disease that plagues human health. It is shown that regular exercise can improve the insulin sensitivity of diabetic patients and have an important function in adjuvant therapy.

Methods: We downloaded the GSE101931 dataset from the Gene Expression Omnibus (GEO) database, 10 samples were obtained from the GSE101931 dataset, including 5 before exercise and 5 postexercise samples, and GEO2R was used to screen the differentially expressed genes (DEGs) exhibited by a heat map. Then, the enrichment analysis of DEGs in Gene Ontology (GO) function was analyzed by Metascape, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of DEGs was also analyzed by gene set enrichment analysis (GSEA). Next, the protein-protein interaction (PPI) network maps were drawn, and the hub genes were identified through Metascape. Finally, the expressions of the hub genes in the dataset were analyzed.

Results: Totally, 116 upregulated DEGs and 1017 downregulated DEGs were identified from these data. These DEGs were mainly enriched in the platelet-derived growth factor receptor signaling pathway and mRNA processing. Then, the GSEA analysis showed that 6 KEGG pathways were associated with postexercise prediabetic samples, namely, ABC transporters, focal adhesion, MAPK signaling pathway, prion diseases, melanogenesis, and gap junction. Afterward, three hub genes (HSPA8, STIP1, and HSPH1) were highly expressed after exercise through the box plot analysis.

Conclusion: A myriad of research results confirms that there is a certain connection between exercise and diabetes, which provides a favorable basis for emerging exercise into the treatment of diabetic patients.

背景:运动是一种有规律的行为活动,不仅有助于减肥,而且可以降低患心脑血管疾病的风险。糖尿病是一种危害人类健康的常见病。研究表明,经常运动可以提高糖尿病患者的胰岛素敏感性,在辅助治疗中具有重要作用。方法:从Gene Expression Omnibus (GEO)数据库下载GSE101931数据集,从GSE101931数据集中获得10个样本,其中5个为运动前样本,5个为运动后样本,使用GEO2R筛选热图显示的差异表达基因(deg)。然后,利用metscape对基因本体(GO)功能中的DEGs进行富集分析,并利用基因集富集分析(GSEA)对DEGs的京都基因与基因组百科全书(KEGG)途径进行分析。下一步,绘制蛋白-蛋白相互作用(PPI)网络图谱,并通过metscape对枢纽基因进行鉴定。最后,对数据集中中心基因的表达进行了分析。结果:从这些数据中共鉴定出116个上调的deg和1017个下调的deg。这些deg主要富集在血小板源性生长因子受体信号通路和mRNA加工中。然后,GSEA分析显示,运动后糖尿病前期样本中有6条KEGG通路相关,即ABC转运蛋白、局灶粘连、MAPK信号通路、朊病毒疾病、黑色素生成和间隙连接。之后,通过箱形图分析,运动后三个枢纽基因(HSPA8、STIP1和HSPH1)高表达。结论:大量的研究结果证实了运动与糖尿病之间存在一定的联系,这为将运动引入糖尿病患者的治疗中提供了有利的依据。
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引用次数: 0
Breast Cancer Prognosis Prediction and Immune Pathway Molecular Analysis Based on Mitochondria-Related Genes 基于线粒体相关基因的乳腺癌预后预测及免疫途径分子分析
IF 1.5 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2022-05-31 DOI: 10.1155/2022/2249909
Weixu Luo, Yuanshan Han, Xin Li, Zhuo Liu, P. Meng, Yuhong Wang
Background Mitochondria play an important role in breast cancer (BRCA). We aimed to build a prognostic model based on mitochondria-related genes. Method Univariate Cox regression analysis, random forest, and the LASSO method were performed in sequence on pretreated TCGA BRCA datasets to screen out genes from a Gene Set Enrichment Analysis, Gene Ontology: biological process gene set to build a prognosis risk score model. Survival analyses and ROC curves were performed to verify the model by using the GSE103091 dataset. The BRCA datasets were equally divided into high- and low-risk score groups. Comparisons between clinical features and immune infiltration related to different risk scores and gene mutation analysis and drug sensitivity prediction were performed for different groups. Result Four genes, MRPL36, FEZ1, BMF, and AFG1L, were screened to construct our risk score model in which the higher the risk score, the poorer the prognosis. Univariate and multivariate analyses showed that the risk score was significantly associated with age, M stage, and N stage. The gene mutation probability in the high-risk score group was significantly higher than that in the low-risk score group. Patients with higher risk scores were more likely to die. Drug sensitivity prediction in different groups indicated that PF-562271 and AS601245 might be new inhibitors of BRCA. Conclusion We developed a new workable risk score model based on mitochondria-related genes for BRCA prognosis and identified new targets and drugs for BRCA research.
线粒体在乳腺癌(BRCA)中起重要作用。我们的目标是建立一个基于线粒体相关基因的预后模型。方法对预处理后的TCGA BRCA数据集依次进行单因素Cox回归分析、随机森林和LASSO方法,从基因集富集分析、基因本体:生物过程基因集中筛选出基因,构建预后风险评分模型。采用GSE103091数据集进行生存分析和ROC曲线验证模型。BRCA数据集平均分为高风险和低风险评分组。比较不同风险评分的临床特征与免疫浸润的关系,并对不同组进行基因突变分析和药物敏感性预测。结果筛选MRPL36、FEZ1、BMF、AFG1L 4个基因构建风险评分模型,风险评分越高,预后越差。单因素和多因素分析显示,风险评分与年龄、M期和N期显著相关。高危评分组基因突变概率显著高于低危评分组。风险评分较高的患者更有可能死亡。不同组药物敏感性预测提示PF-562271和AS601245可能是新的BRCA抑制剂。结论建立了一种新的基于线粒体相关基因的BRCA预后风险评分模型,并确定了BRCA研究的新靶点和药物。
{"title":"Breast Cancer Prognosis Prediction and Immune Pathway Molecular Analysis Based on Mitochondria-Related Genes","authors":"Weixu Luo, Yuanshan Han, Xin Li, Zhuo Liu, P. Meng, Yuhong Wang","doi":"10.1155/2022/2249909","DOIUrl":"https://doi.org/10.1155/2022/2249909","url":null,"abstract":"Background Mitochondria play an important role in breast cancer (BRCA). We aimed to build a prognostic model based on mitochondria-related genes. Method Univariate Cox regression analysis, random forest, and the LASSO method were performed in sequence on pretreated TCGA BRCA datasets to screen out genes from a Gene Set Enrichment Analysis, Gene Ontology: biological process gene set to build a prognosis risk score model. Survival analyses and ROC curves were performed to verify the model by using the GSE103091 dataset. The BRCA datasets were equally divided into high- and low-risk score groups. Comparisons between clinical features and immune infiltration related to different risk scores and gene mutation analysis and drug sensitivity prediction were performed for different groups. Result Four genes, MRPL36, FEZ1, BMF, and AFG1L, were screened to construct our risk score model in which the higher the risk score, the poorer the prognosis. Univariate and multivariate analyses showed that the risk score was significantly associated with age, M stage, and N stage. The gene mutation probability in the high-risk score group was significantly higher than that in the low-risk score group. Patients with higher risk scores were more likely to die. Drug sensitivity prediction in different groups indicated that PF-562271 and AS601245 might be new inhibitors of BRCA. Conclusion We developed a new workable risk score model based on mitochondria-related genes for BRCA prognosis and identified new targets and drugs for BRCA research.","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2022-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47525843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Association of Endothelin-Converting Enzyme and Endothelin-1 Gene Polymorphisms with Essential Hypertension in Malay Ethnics 内皮素转换酶和内皮素-1基因多态性与马来族原发性高血压的关系
IF 1.5 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2022-05-16 DOI: 10.1155/2022/9129960
Elnaz Salim, V. Ramachandran, Neda Ansari, P. Ismail, M. H. Mohamed, N. Mohamad, Liyana Najwa Inche Mat
Objectives Endothelin-1 (ET-1), the most potent endogenous vasoconstrictor, generated by enzymatic cleavage catalyzed by an endothelin-converting enzyme (ECE), plays a significant role in the regulation of hypertension. Methods This study investigates the effect of endothelin-1 (Lys198Asn/rs5370) and ECE (rs212526 C/T) gene polymorphisms with essential hypertension (EH) among Malay ethnics. To determine the association of gene polymorphism, 177 hypertensives and controls (196) were genotyped using Taqman method. Results A significant difference was observed in ET-1 rs5370 and ECE rs212526 gene polymorphisms between EH and control subjects (P < 0.001). A significantly high body mass index (BMI), waist-to-hip ratio, fasting plasma glucose, hemoglobin A1c, systolic and diastolic blood pressure, and lipid profiles were observed among the EH patients when compared to controls (P < 0.05). Moreover, T allele (rs5370) carriers in males have a high risk for EH. There was no significant association between gender in ECE C/T polymorphisms (P > 0.05). Conclusion Based on our result, it is evident that the T allele of ET-1 rs5370 polymorphism and C allele of ECE rs212526 have a significant genetic risk factor in EH among Malay subjects, and BMI and age are associated with hypertension.
目的内皮素-1(ET-1)是内皮素转化酶(ECE)催化酶切产生的最有效的内源性血管收缩剂,在高血压的调节中发挥重要作用。方法探讨内皮素-1(Lys198Asn/rs5370)和ECE(rs212526C/T)基因多态性与马来族原发性高血压(EH)的关系。为了确定基因多态性的相关性,使用Taqman方法对177名高血压患者和对照组(196)进行了基因分型。结果EH患者ET-1 rs5370和ECE rs212526基因多态性与对照组比较有显著性差异(P<0.001)。EH患者的体重指数(BMI)、腰臀比、空腹血糖、血红蛋白A1c、收缩压和舒张压以及血脂水平均显著高于对照组(P<0.05),男性T等位基因(rs5370)携带者是EH的高危人群,ECE C/T多态性与性别无显著相关性(P>0.05)。
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引用次数: 2
The Bioinformatical Identification of Potential Biomarkers in Heart Failure Diagnosis and Treatment 心力衰竭诊断和治疗中潜在生物标志物的生物信息学鉴定
IF 1.5 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2022-05-16 DOI: 10.1155/2022/8727566
Xiaodong Sheng, Xiaoqi Jin, Yanqi Liu, Tao Fan, Zongcheng Zhu, Jing Jin, Guanqun Zheng, Zhixian Chen, Min Lu, Zhiqiang Wang
Background Heart failure (HF) is defined as the inability of the heart's systolic and diastolic function to properly discharge blood flow from the veins to the heart. The goal of our research is to look into the possible mechanism that causes HF. Methods The GSE5406 database was used for screening the differentially expressed genes (DEGs). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) network were applied to analyze DEGs. Besides, cell counting Kit-8 (CCK-8) was conducted to observe the knockdown effect of hub genes on cell proliferation. Results Finally, 377 upregulated and 461 downregulated DEGs came out, enriched in the extracellular matrix organization and gap junction. According to GSEA results, Hoft cd4 positive alpha beta memory t cell bcg vaccine age 18–45 yo id 7 dy top 100 deg ex vivo up, Sobolev t cell pandemrix age 18–64 yo 7 dy dn, and so on were significantly related to gene set GSE5406. 7 hub genes, such as COL1A1, UBB, COL3A1, HSP90AA1, MYC, STAT3 and MAPK1, were selected from PPI networks. CCK-8 indicated silencing of STAT3 promoted the proliferation of H9C2 cells and silencing of UBB inhibited the proliferation of H9C2 cells. Conclusion Our analysis reveals that COL1A1, UBB, COL3A1, HSP90AA1, MYC, STAT3, and MAPK1 might promote the progression of HF and become the biomarkers for diagnosis and treatment of HF.
背景心力衰竭(HF)是指心脏的收缩和舒张功能无法将血液从静脉正确排出到心脏。本研究的目的是探讨HF的可能机制。方法利用GSE5406数据库筛选差异表达基因。应用基因本体论(GO)、京都基因与基因组百科全书(KEGG)和蛋白质-蛋白质相互作用(PPI)网络对DEG进行分析。此外,通过细胞计数Kit-8(CCK-8)观察hub基因对细胞增殖的敲除作用。结果共产生377个上调和461个下调的DEG,富集于细胞外基质组织和间隙连接。根据GSEA结果,Hoft cd4阳性α-β记忆t细胞bcg疫苗年龄为18-45岁 yo-id 7 dy top 100 deg离体向上,Sobolev t细胞pandemrix年龄18-64岁 yo 7 dy-dn等与基因集GSE5406显著相关。从PPI网络中筛选出COL1A1、UBB、COL3A1、HSP90AA1、MYC、STAT3和MAPK1等7个枢纽基因。CCK-8表明STAT3的沉默促进H9C2细胞的增殖,而UBB的沉默抑制H9C2的增殖。结论COL1A1、UBB、COL3A1、HSP90AA1、MYC、STAT3和MAPK1可能促进HF的进展,成为诊断和治疗HF的生物标志物。
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引用次数: 2
Analysis of the lncRNA-Associated Competing Endogenous RNA (ceRNA) Network for Tendinopathy lncrna相关的内源性竞争RNA (ceRNA)网络在肌腱病变中的作用分析
IF 1.5 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2022-05-12 DOI: 10.1155/2022/9792913
Bing-Zhe Huang, Yang Jing-Jing, Xiao-Ming Dong, Zhuan Zhong, Xiao-Ning Liu
Background We aimed to construct the lncRNA-associated competing endogenous RNA (ceRNA) network and distinguish feature lncRNAs associated with tendinopathy. Methods We downloaded the gene profile of GSE26051 from the Gene Expression Omnibus (GEO), including 23 normal samples and 23 diseased tendons. Differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) were identified, and functional and pathway enrichment analyses were performed. Protein-protein interaction (PPI) network was constructed and further analyzed by module mining. Moreover, a ceRNA regulatory network was constructed based on the identified lncRNA–mRNA coexpression relationship pairs and miRNA–mRNA regulation pairs. Results We identified 1117 DEmRNAs and 57 DElncRNAs from the GEO data. The downregulated DEmRNAs were particularly associated with muscle contraction and muscle filament, while the upregulated ones were linked to extracellular matrix organization and cell adhesion. From the PPI network, 11 modules were extracted. Genes in MCODE 2 (such as TPM4) were significantly involved in cardiomyopathy, and genes in MCODE 4 (such as COL4A3 and COL4A4) were involved in focal adhesion, ECM-receptor interaction, and PI3K-Akt signaling pathway. The ceRNA network contained 7 lncRNAs (MIR133A1HG, LINC01405, PRKCQ-AS1, C10orf71-AS1, MBNL1-AS1, HOTAIRM1, and DNM3OS), 63 mRNAs, and 41 miRNAs. Downregulated lncRNA MIR133A1HG could competitively bind with hsa-miR-659-3p and hsa-miR-218-1-3p to regulate the TPM3. Meanwhile, MIR133A1HG could competitively bind with hsa-miR-1179 to regulate the COL4A3. Downregulated C10orf71-AS1 could competitively bind with hsa-miR-130a-5p to regulate the COL4A4. Conclusions Seven important lncRNAs, particularly MIR133A1HG and C10orf71-AS1, were found associated with tendinopathy according to the lncRNA-associated ceRNA network.
背景我们旨在构建lncRNA相关竞争内源性RNA(ceRNA)网络,并区分与腱病相关的特征lncRNA。方法从基因表达综合库(GEO)下载GSE26051基因图谱,包括23个正常肌腱和23个病变肌腱。鉴定了差异表达的mRNA(DEmRNA)和差异表达的lncRNA(DElncRNA),并进行了功能和途径富集分析。构建了蛋白质-蛋白质相互作用(PPI)网络,并通过模块挖掘进行了进一步分析。此外,基于已鉴定的lncRNA-mRNA共表达关系对和miRNA-mRNA调控对构建了ceRNA调控网络。结果我们从GEO数据中鉴定出1117个DEmRNA和57个DElncRNA。下调的DEmRNA与肌肉收缩和肌丝特别相关,而上调的DEmRNAs与细胞外基质组织和细胞粘附有关。从PPI网络中提取了11个模块。MCODE 2中的基因(如TPM4)显著参与心肌病,MCODE 4中的基因(例如COL4A3和COL4A4)参与局灶粘附、ECM受体相互作用和PI3K-Akt信号通路。ceRNA网络包含7个lncRNA(MIR133A1HG、LINC01405、PRKCQ-AS1、C10orf71-AS1、MBNL1-AS1、HOTAIRM1和DNM3OS)、63个mRNA和41个miRNA。下调的lncRNA MIR133A1HG可以与hsa-miR-659-3p和hsa-miR-218-1-3p竞争性结合以调节TPM3。同时,MIR133A1HG可以与hsa-miR-1179竞争性结合以调节COL4A3。下调的C10orf71-AS1可以与hsa-miR-130a-5p竞争性结合以调节COL4A4。结论根据lncRNA相关的ceRNA网络,发现7种重要的lncRNA,特别是MIR133A1HG和C10orf71-AS1与腱病相关。
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引用次数: 0
Scrutinizing Deleterious Nonsynonymous SNPs and Their Effect on Human POLD1 Gene 审查有害的非同义snp及其对人类POLD1基因的影响
IF 1.5 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2022-05-11 DOI: 10.1155/2022/1740768
Md. Nazmul Islam Bappy, Anindita Roy, Md Gulam Rabbany Rabbi, Nusrat Jahan, Fahmida Akther Chowdhury, Syeda Farjana Hoque, E. Sajib, Parvez Khan, F. Hossain, K. Zinnah
POLD1 (DNA polymerase delta 1, catalytic subunit) is a protein-coding gene that encodes the large catalytic subunit (POLD1/p125) of the DNA polymerase delta (Polδ) complex. The consequence of missense or nonsynonymous SNPs (nsSNPs), which occur in the coding region of a specific gene, is the replacement of single amino acid. It may also change the structure, stability, and/or functions of the protein. Mutation in the POLD1 gene is associated with autosomal dominant predisposition to colonic adenomatous polyps, colon cancer, endometrial cancer (EDMC), breast cancer, and brain tumors. These de novo mutations in the POLD1 gene also result in autosomal dominant MDPL syndrome (mandibular hypoplasia, deafness, progeroid features, and lipodystrophy). In this study, genetic variations of POLD1 which may affect the structure and/or function were analyzed using different types of bioinformatics tools. A total of 17038 nsSNPs for POLD1 were collected from the NCBI database, among which 1317 were missense variants. Out of all missense nsSNPs, 28 were found to be deleterious functionally and structurally. Among these deleterious nsSNPs, 23 showed a conservation scale of >5, 2 were predicted to be associated with binding site formation, and one acted as a posttranslational modification site. All of them were involved in coil, extracellular structures, or helix formation, and some cause the change in size, charge, and hydrophobicity.
POLD1(DNA聚合酶δ1,催化亚基)是一种蛋白质编码基因,编码DNA聚合酶δ(Polδ)复合物的大催化亚基(POLD1/p125)。出现在特定基因编码区的错义或非同义SNPs(nsSNPs)的结果是替换单个氨基酸。它还可以改变蛋白质的结构、稳定性和/或功能。POLD1基因突变与结肠腺瘤性息肉、结肠癌癌症、癌症(EDMC)、癌症和脑肿瘤的常染色体显性遗传易感性相关。POLD1基因的这些新突变也会导致常染色体显性MDPL综合征(下颌发育不全、耳聋、类激素特征和脂肪营养不良)。在本研究中,使用不同类型的生物信息学工具分析了可能影响POLD1结构和/或功能的遗传变异。从NCBI数据库中总共收集了17038个POLD1的nsSNPs,其中1317个是错义变体。在所有错义nsSNPs中,有28个被发现在功能和结构上是有害的。在这些有害的nsSNPs中,23个表现出>5的保守性,2个被预测与结合位点的形成有关,1个作为翻译后修饰位点。它们都参与了螺旋、细胞外结构或螺旋的形成,其中一些导致了大小、电荷和疏水性的变化。
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引用次数: 2
Genome-Wide Identification and Functional Analysis of Lysine Histidine Transporter (LHT) Gene Families in Maize 玉米赖氨酸组氨酸转运蛋白(LHT)基因家族的全基因组鉴定和功能分析
IF 1.5 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2022-04-26 DOI: 10.1155/2022/2673748
Md Golam Rabby, M. Hossen, M. Kamal, Md Numan Islam
Amino acid transporters (AATs) are essential membrane proteins that transfer amino acids across cells. They are necessary for plant growth and development. The lysine histidine transporter (LHT) gene family in maize (Zea mays) has not yet been characterized. According to sequence composition and phylogenetic placement, this study found 15 LHT genes in the maize genome. The ZmLHT genes are scattered across the plasma membrane. The study also analyzed the evolutionary relationships, gene structures, conserved motifs, 3D protein structure, a transmembrane domain, and gene expression of the 15 LHT genes in maize. Comprehensive analyses of ZmLHT gene expression profiles revealed distinct expression patterns in maize LHT genes in various tissues. This study's extensive data will serve as a foundation for future ZmLHT gene family research. This study might make easier to understand how LHT genes work in maize and other crops.
氨基酸转运蛋白(AATs)是跨细胞传递氨基酸的重要膜蛋白。它们是植物生长发育所必需的。玉米赖氨酸组氨酸转运蛋白(LHT)基因家族尚未被鉴定。根据序列组成和系统发育位置,本研究在玉米基因组中发现了15个LHT基因。ZmLHT基因散布在质膜上。该研究还分析了玉米中15个LHT基因的进化关系、基因结构、保守基序、3D蛋白结构、跨膜结构域和基因表达。ZmLHT基因表达谱的综合分析揭示了玉米LHT基因在不同组织中的不同表达模式。这项研究的大量数据将为未来的ZmLHT基因家族研究奠定基础。这项研究可能更容易理解LHT基因在玉米和其他作物中的作用。
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引用次数: 3
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Genetics research
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