Pan‐cancer analyses of bromodomain containing 9 as a novel therapeutic target reveals its diagnostic, prognostic potential and biological mechanism in human tumours

机制(生物学) 癌症 医学 溴尿嘧啶 肿瘤科 计算生物学 癌症研究 生物信息学 内科学 生物 表观遗传学 遗传学 基因 哲学 认识论
作者
Yu Chen,Zitong Gao,Isam Mohd‐Ibrahim,Hua Yang,Lang Wu,Xiaoying Fan,Youping Deng
出处
期刊:Clinical and translational medicine [Wiley]
卷期号:14 (2) 被引量:2
标识
DOI:10.1002/ctm2.1543
摘要

Abstract Background Mutations in one or more genes responsible for encoding subunits within the SWItch/Sucrose Non‐Fermentable (SWI/SNF) chromatin‐remodelling complexes are found in approximately 25% of cancer patients. Bromodomain containing 9 ( BRD9 ) is a more recently identified protein coding gene, which can encode SWI/SNF chromatin‐remodelling complexes subunits. Although initial evaluations of the potential of BRD9‐based targeted therapy have been explored in the clinical application of a small number of cancer types, more detailed study of the diagnostic and prognostic potential, as well as the detailed biological mechanism of BRD9 remains unreported. Methods We used various bioinformatics tools to generate a comprehensive, pan‐cancer analyses of BRD9 expression in multiple disease types described in The Cancer Genome Atlas (TCGA). Experimental validation was conducted in tissue microarrays and cell lines derived from lung and colon cancers. Results Our study revealed that BRD9 exhibited elevated expression in a wide range of tumours. Analysis of survival data and DNA methylation for BRD9 indicated distinct conclusions for multiple tumours. mRNA splicing and molecular binding were involved in the functional mechanism of BRD9 . BRD9 may affect cancer progression through different phosphorylation sites or N 6 ‐methyladenosine site modifications. BRD9 could potentially serve as a novel biomarker for diagnosing different cancer types, especially could accurately forecast the prognosis of melanoma patients receiving anti‐programmed cell death 1 immunotherapy. BRD9 has the potential to serve as a therapeutic target, when pairing with etoposide in patients with melanoma. The BRD9/SMARCD1 axis exhibited promising discriminative performance in forecasting the prognosis of patients afflicted with liver hepatocellular carcinoma (LIHC) and mesothelioma. Additionally, this axis appears to potentially influence the immune response in LIHC by regulating the programmed death‐ligand 1 immune checkpoint. For experimental validation, high expression levels of BRD9 were observed in tumour tissue samples from both lung and colon cancer patients. Knocking down BRD9 led to the inhibition of lung and colon cancer development, likely via the Wnt/β‐catenin signalling pathway. Conclusions These pan‐cancer study revealed the diagnostic and prognostic potential, along with the biological mechanism of BRD9 as a novel therapeutic target in human tumours.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
一独白完成签到 ,获得积分10
1秒前
1秒前
3秒前
GOD伟完成签到,获得积分10
4秒前
识途完成签到 ,获得积分10
4秒前
充电宝应助典雅的蜡烛采纳,获得10
5秒前
5秒前
LTY完成签到,获得积分10
5秒前
小铭的男仆完成签到,获得积分20
5秒前
热心的冷松完成签到,获得积分10
6秒前
勤奋的花前茶完成签到,获得积分10
7秒前
大尾巴白完成签到,获得积分10
7秒前
7秒前
7秒前
qq发布了新的文献求助10
8秒前
9秒前
蝈蝈完成签到,获得积分10
10秒前
cmq完成签到 ,获得积分10
10秒前
李健应助¥#¥-11采纳,获得10
11秒前
骤雨时晴完成签到 ,获得积分10
11秒前
11秒前
熠旅完成签到,获得积分10
11秒前
温暖宛筠完成签到,获得积分10
12秒前
爆米花应助HalaMadrid采纳,获得10
12秒前
12秒前
CY03发布了新的文献求助10
13秒前
豌豆发布了新的文献求助10
13秒前
今何在完成签到,获得积分10
13秒前
14秒前
15秒前
Lin完成签到,获得积分10
16秒前
17秒前
17秒前
桐桐应助明亮访烟采纳,获得10
17秒前
ccmia发布了新的文献求助10
18秒前
李健的小迷弟应助丫丫采纳,获得10
18秒前
Dawn发布了新的文献求助10
18秒前
Frank应助FFFY采纳,获得10
18秒前
Hiker发布了新的文献求助10
19秒前
小苑完成签到,获得积分10
20秒前
高分求助中
Comparative Anatomy of the Vertebrates 9th 3000
Continuum Thermodynamics and Material Modelling 3000
Production Logging: Theoretical and Interpretive Elements 2700
Les Mantodea de Guyane Insecta, Polyneoptera 1000
Structural Load Modelling and Combination for Performance and Safety Evaluation 1000
Conference Record, IAS Annual Meeting 1977 820
England and the Discovery of America, 1481-1620 600
热门求助领域 (近24小时)
化学 材料科学 生物 医学 工程类 有机化学 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 量子力学 光电子学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3571872
求助须知:如何正确求助?哪些是违规求助? 3142287
关于积分的说明 9446687
捐赠科研通 2843683
什么是DOI,文献DOI怎么找? 1562971
邀请新用户注册赠送积分活动 731530
科研通“疑难数据库(出版商)”最低求助积分说明 718557