Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer.

IF 1.7 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL
Open Medicine Pub Date : 2024-07-17 eCollection Date: 2024-01-01 DOI:10.1515/med-2024-0997
Xiaoxia Tong, Li Ma, Di Wu, Yibing Liu, Yonglei Liu
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引用次数: 0

Abstract

Backgrounds: The integrator complex (INT) is a multiprotein assembly in gene transcription. Although several subunits of INT complex have been implicated in multiple cancers, the complex's role in gastric cancer (GC) is poorly understood.

Methods: The gene expressions, prognostic values, and the associations with microsatellite instability (MSI) of INT subunits were confirmed by GEO and The Cancer Genome Atlas (TCGA) databases. cBioPortal, GeneMANIA, TISIDB, and MCPcounter algorithm were adopted to investigate the mutation frequency, protein-protein interaction network, and the association with immune cells of INT subunits in GC. Additionally, in vitro experiments were performed to confirm the role of INTS11 in pathogenesis of GC.

Results: The mRNA expression levels of INTS2/4/5/7/8/9/10/11/12/13/14 were significantly elevated both in GSE183904 and TCGA datasets. Through functional enrichment analysis, the functions of INT subunits were mainly associated with snRNA processing, INT, and DNA-directed 5'-3' RNA polymerase activity. Moreover, these INT subunit expressions were associated with tumor-infiltrating lymphocytes and MSI in GC. In vitro experiments demonstrated that knockdown of the catalytic core INTS11 in GC cells inhibits cell proliferation ability. INTS11 overexpression showed opposite effects.

Conclusions: Our data demonstrate that the INT complex might act as an oncogene and can be used as a prognosis biomarker for GC.

胃癌整合器复合体亚基的综合图谱及其与预后和肿瘤微环境的关系
背景:整合子复合体(INT)是基因转录过程中的多蛋白集合体。尽管INT复合物的几个亚基与多种癌症有关联,但该复合物在胃癌(GC)中的作用却鲜为人知:采用cBioPortal、GeneMANIA、TISIDB和MCPcounter算法研究INT亚基在胃癌中的突变频率、蛋白相互作用网络以及与免疫细胞的关联。此外,还通过体外实验证实了INTS11在GC发病机制中的作用:结果:INTS2/4/5/7/8/9/10/11/12/13/14的mRNA表达水平在GSE183904和TCGA数据集中均显著升高。通过功能富集分析,INT 亚基的功能主要与 snRNA 处理、INT 和 DNA 定向 5'-3' RNA 聚合酶活性有关。此外,这些INT亚基的表达与肿瘤浸润淋巴细胞和GC中的MSI有关。体外实验表明,GC 细胞中催化核心 INTS11 的敲除会抑制细胞的增殖能力。结论:我们的数据表明,INT 复合物可能是一种癌基因,可用作 GC 的预后生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Open Medicine
Open Medicine Medicine-General Medicine
CiteScore
3.00
自引率
0.00%
发文量
153
审稿时长
20 weeks
期刊介绍: Open Medicine is an open access journal that provides users with free, instant, and continued access to all content worldwide. The primary goal of the journal has always been a focus on maintaining the high quality of its published content. Its mission is to facilitate the exchange of ideas between medical science researchers from different countries. Papers connected to all fields of medicine and public health are welcomed. Open Medicine accepts submissions of research articles, reviews, case reports, letters to editor and book reviews.
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