{"title":"在肺腺癌中,INTS7通过促进细胞周期进程调节细胞增殖和凋亡。","authors":"Yaming Liu, Tengfei Huang, Dehua Zeng, Meiqing Zhang, Duohuan Lian, Shunkai Zhou, Mengmeng Chen, Zhiyong Zeng, Huizhong Li","doi":"10.1093/bfgp/elaf014","DOIUrl":null,"url":null,"abstract":"<p><p>The evolutionarily conserved Integrator complex, which is composed of over 10 subunits, orchestrates diverse RNA-processing events such as 3'-end maturation of small nuclear RNAs (snRNAs), transcription termination of RNA Polymerase II, and DNA damage response signaling pathways; however, the functional roles of individual Integrator complex subunits in lung adenocarcinoma (LUAD) remain poorly characterized, and this study aimed to systematically investigate the potential oncogenic functions and prognostic values of these subunits in LUAD. To achieve this goal, the expression profiles of Integrator complex subunits were profiled using transcriptomic data from the The Cancer Genome Atlas (TCGA) database, survival analyses (including Kaplan-Meier and Cox regression models) were performed to evaluate the correlations between subunit expression levels and patient survival outcomes (overall survival (OS) and disease-free survival (DFS)), co-expression network analysis was conducted to annotate the potential biological functions of key subunits, and functional validation was performed using CCK-8 assays and flow cytometry to assess the impact of INTS7 depletion on cell proliferation and cycle progression in LUAD cell lines. The findings of this study showed that Integrator complex subunits were significantly overexpressed in LUAD tissues compared to normal lung parenchyma; among these subunits, INTS7 expression was most strongly associated with shortened OS and DFS, indicating its pivotal role in LUAD pathogenesis, while bioinformatics analyses revealed that INTS7 is involved in regulating critical biological processes including cell cycle progression, transcriptional regulation, and RNA metabolism, and loss-of-function experiments demonstrated that genetic silencing of INTS7 significantly inhibited cell proliferation and induced cell cycle arrest in LUAD cells. Ultimately, this study provides the first evidence that INTS7, a core component of the Integrator complex, serves as a functional and prognostic regulator in LUAD, highlighting its potential as a therapeutic target for this malignancy.</p>","PeriodicalId":55323,"journal":{"name":"Briefings in Functional Genomics","volume":"24 ","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12393144/pdf/","citationCount":"0","resultStr":"{\"title\":\"INTS7 modulates cell proliferation and apoptosis via promoting cell cycle progression in lung adenocarcinoma.\",\"authors\":\"Yaming Liu, Tengfei Huang, Dehua Zeng, Meiqing Zhang, Duohuan Lian, Shunkai Zhou, Mengmeng Chen, Zhiyong Zeng, Huizhong Li\",\"doi\":\"10.1093/bfgp/elaf014\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The evolutionarily conserved Integrator complex, which is composed of over 10 subunits, orchestrates diverse RNA-processing events such as 3'-end maturation of small nuclear RNAs (snRNAs), transcription termination of RNA Polymerase II, and DNA damage response signaling pathways; however, the functional roles of individual Integrator complex subunits in lung adenocarcinoma (LUAD) remain poorly characterized, and this study aimed to systematically investigate the potential oncogenic functions and prognostic values of these subunits in LUAD. To achieve this goal, the expression profiles of Integrator complex subunits were profiled using transcriptomic data from the The Cancer Genome Atlas (TCGA) database, survival analyses (including Kaplan-Meier and Cox regression models) were performed to evaluate the correlations between subunit expression levels and patient survival outcomes (overall survival (OS) and disease-free survival (DFS)), co-expression network analysis was conducted to annotate the potential biological functions of key subunits, and functional validation was performed using CCK-8 assays and flow cytometry to assess the impact of INTS7 depletion on cell proliferation and cycle progression in LUAD cell lines. The findings of this study showed that Integrator complex subunits were significantly overexpressed in LUAD tissues compared to normal lung parenchyma; among these subunits, INTS7 expression was most strongly associated with shortened OS and DFS, indicating its pivotal role in LUAD pathogenesis, while bioinformatics analyses revealed that INTS7 is involved in regulating critical biological processes including cell cycle progression, transcriptional regulation, and RNA metabolism, and loss-of-function experiments demonstrated that genetic silencing of INTS7 significantly inhibited cell proliferation and induced cell cycle arrest in LUAD cells. Ultimately, this study provides the first evidence that INTS7, a core component of the Integrator complex, serves as a functional and prognostic regulator in LUAD, highlighting its potential as a therapeutic target for this malignancy.</p>\",\"PeriodicalId\":55323,\"journal\":{\"name\":\"Briefings in Functional Genomics\",\"volume\":\"24 \",\"pages\":\"\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-01-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12393144/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Briefings in Functional Genomics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1093/bfgp/elaf014\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Briefings in Functional Genomics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/bfgp/elaf014","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
INTS7 modulates cell proliferation and apoptosis via promoting cell cycle progression in lung adenocarcinoma.
The evolutionarily conserved Integrator complex, which is composed of over 10 subunits, orchestrates diverse RNA-processing events such as 3'-end maturation of small nuclear RNAs (snRNAs), transcription termination of RNA Polymerase II, and DNA damage response signaling pathways; however, the functional roles of individual Integrator complex subunits in lung adenocarcinoma (LUAD) remain poorly characterized, and this study aimed to systematically investigate the potential oncogenic functions and prognostic values of these subunits in LUAD. To achieve this goal, the expression profiles of Integrator complex subunits were profiled using transcriptomic data from the The Cancer Genome Atlas (TCGA) database, survival analyses (including Kaplan-Meier and Cox regression models) were performed to evaluate the correlations between subunit expression levels and patient survival outcomes (overall survival (OS) and disease-free survival (DFS)), co-expression network analysis was conducted to annotate the potential biological functions of key subunits, and functional validation was performed using CCK-8 assays and flow cytometry to assess the impact of INTS7 depletion on cell proliferation and cycle progression in LUAD cell lines. The findings of this study showed that Integrator complex subunits were significantly overexpressed in LUAD tissues compared to normal lung parenchyma; among these subunits, INTS7 expression was most strongly associated with shortened OS and DFS, indicating its pivotal role in LUAD pathogenesis, while bioinformatics analyses revealed that INTS7 is involved in regulating critical biological processes including cell cycle progression, transcriptional regulation, and RNA metabolism, and loss-of-function experiments demonstrated that genetic silencing of INTS7 significantly inhibited cell proliferation and induced cell cycle arrest in LUAD cells. Ultimately, this study provides the first evidence that INTS7, a core component of the Integrator complex, serves as a functional and prognostic regulator in LUAD, highlighting its potential as a therapeutic target for this malignancy.
期刊介绍:
Briefings in Functional Genomics publishes high quality peer reviewed articles that focus on the use, development or exploitation of genomic approaches, and their application to all areas of biological research. As well as exploring thematic areas where these techniques and protocols are being used, articles review the impact that these approaches have had, or are likely to have, on their field. Subjects covered by the Journal include but are not restricted to: the identification and functional characterisation of coding and non-coding features in genomes, microarray technologies, gene expression profiling, next generation sequencing, pharmacogenomics, phenomics, SNP technologies, transgenic systems, mutation screens and genotyping. Articles range in scope and depth from the introductory level to specific details of protocols and analyses, encompassing bacterial, fungal, plant, animal and human data.
The editorial board welcome the submission of review articles for publication. Essential criteria for the publication of papers is that they do not contain primary data, and that they are high quality, clearly written review articles which provide a balanced, highly informative and up to date perspective to researchers in the field of functional genomics.