三方基序(TRIM)家族分子特征的研究以及 TRIM31 在胃癌中的初步验证。

IF 3.8 3区 医学 Q2 GENETICS & HEREDITY
Yixin Ding, Yangyang Lu, Jing Guo, Shuming Chen, Xiaoxi Han, Shibo Wang, Mengqi Zhang, Rui Wang, Jialin Song, Kongjia Wang, Wensheng Qiu, Weiwei Qi
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引用次数: 0

摘要

大多数 TRIM 家族成员都是 E3 泛素连接酶,参与泛素化和肿瘤发生。但目前还缺乏对胃癌(GC)中整个家族成员的全面调查。通过结合TCGA和GEO数据库,我们获得了常见的TRIM家族成员(TRIMs),以研究基因表达、基因突变和临床预后。在TRIMs的基础上,进行了共识聚类分析,并建立了风险评估系统和预后模型。特别是选择了具有临床预后和诊断价值的 TRIM31 进行单基因生物信息学分析、体外实验验证和临床组织芯片免疫组化分析。合并数据集包括 66 个 TRIMs,其中 52 个具有差异表达,43 个具有差异预后。通过共识聚类分析获得的基因簇之间存在显著的生存差异。利用多元 Cox 回归和 LASSO 回归确定的 4 个差异表达基因,建立了一个风险评分系统。较高的风险评分与较差的预后、抑制性免疫细胞浸润和耐药性有关。转录组数据和临床样本组织芯片证实,TRIM31在GC中高表达,并与不良预后相关。通路富集分析、细胞迁移和集落形成测定、EdU测定、活性氧(ROS)测定和线粒体膜电位测定显示,TRIM31可能与细胞周期调控和氧化应激相关通路有关,并导致胃癌的发生。本研究调查了 TRIM31 家族在胃癌中的整个功能和表达谱以及基于 TRIM31 家族的风险评分系统。围绕 TRIM31 开展的进一步研究有助于深入了解其家族其他成员在胃癌中的潜在作用机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An investigation of the molecular characterization of the tripartite motif (TRIM) family and primary validation of TRIM31 in gastric cancer.

Most TRIM family members characterized by the E3-ubiquitin ligases, participate in ubiquitination and tumorigenesis. While there is a dearth of a comprehensive investigation for the entire family in gastric cancer (GC). By combining the TCGA and GEO databases, common TRIM family members (TRIMs) were obtained to investigate gene expression, gene mutations, and clinical prognosis. On the basis of TRIMs, a consensus clustering analysis was conducted, and a risk assessment system and prognostic model were developed. Particularly, TRIM31 with clinical prognostic and diagnostic value was chosen for single-gene bioinformatics analysis, in vitro experimental validation, and immunohistochemical analysis of clinical tissue microarrays. The combined dataset consisted of 66 TRIMs, of which 52 were differentially expressed and 43 were differentially prognostic. Significant survival differences existed between the gene clusters obtained by consensus clustering analysis. Using 4 differentially expressed genes identified by multivariate Cox regression and LASSO regression, a risk scoring system was developed. Higher risk scores were associated with a poorer prognosis, suppressive immune cell infiltration, and drug resistance. Transcriptomic data and clinical sample tissue microarrays confirmed that TRIM31 was highly expressed in GC and associated with a poor prognosis. Pathway enrichment analysis, cell migration and colony formation assay, EdU assay, reactive oxygen species (ROS) assay, and mitochondrial membrane potential assay revealed that TRIM31 may be implicated in cell cycle regulation and oxidative stress-related pathways, contribute to gastric carcinogenesis. This study investigated the whole functional and expression profile and a risk score system based on the TRIM family in GC. Further investigation centered around TRIM31 offers insight into the underlying mechanisms of action exhibited by other members of its family in the context of GC.

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来源期刊
Human Genomics
Human Genomics GENETICS & HEREDITY-
CiteScore
6.00
自引率
2.20%
发文量
55
审稿时长
11 weeks
期刊介绍: Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.
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