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Global transcriptional downregulation of TREX and nuclear trafficking machinery as pan-senescence phenomena: evidence from human cells and tissues

Title
Global transcriptional downregulation of TREX and nuclear trafficking machinery as pan-senescence phenomena: evidence from human cells and tissues
Authors
Kim, Sung YoungYang, Eun JaeLee, Sung BaeLee, Young-SamCho, Kyoung A.Park, Sang Chul
DGIST Authors
Kim, Sung Young; Yang, Eun Jae; Lee, Sung BaeLee, Young-Sam; Cho, Kyoung A.; Park, Sang Chul
Issue Date
2020-08
Citation
Experimental and Molecular Medicine, 52(8), 1351-1359
Type
Article
Article Type
Article
Keywords
TUMOR-SUPPRESSORPORE COMPLEXMECHANISMSEXPRESSIONCANCERGENE
ISSN
1226-3613
Abstract
Nucleocytoplasmic trafficking (NCT) of macromolecules is a fundamental process in eukaryotes that requires tight controls to maintain proper cell functions. Downregulation of the classical NCT pathway in senescent cells has been reported. However, whether this is a hallmark that exists across all types of cellular senescence remains unknown, and whether the mRNA export machinery is altered during senescence has not been demonstrated. Here, we show that the global transcriptomic downregulation of both the TREX (transcription-export) machinery and classical NLS-dependent protein transport machinery is a hallmark of varying types of senescence. A gene set-based approach using 25 different studies showed that the TREX-NCT gene set displays distinct common downregulated patterns in senescent cells versus its expression in their nonsenescent counterparts regardless of the senescence type, such as replicative senescence (RS), tumor cell senescence (TCS), oncogene-induced senescence (OIS), stem cell senescence (SCS), progeria and endothelial cell senescence (ECS). Similar patterns of TREX-NCT gene downregulation were also shown in two large human tissue genomic databases, the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. We also found that early-stage cancer tissues show consistent age-related patterns of TREX-NCT enrichment, suggesting the potential significance of TREX-NCT genes in determining cell fate in the early stage of tumorigenesis. Moreover, human cancer tissues exhibit an opposite TREX-NCT enrichment pattern with aging, indicating that deviation from age-related changes in TREX-NCT genes may provide a novel but critical clue for the age-dependent pathogenesis of cancer and increase in cancer incidence with aging. © 2020, The Author(s).
URI
http://hdl.handle.net/20.500.11750/12400
DOI
10.1038/s12276-020-00490-x
Publisher
Springer Nature
Related Researcher
  • Author Lee, Sung Bae Laboratory of Neurodegenerative Diseases and Aging
  • Research Interests Cellular mechanism of neurodegenerative diseases; Neuronal maintenance and remodeling; 퇴행성 뇌질환의 세포기전; 신경계 유지 및 리모델링 연구
Files:
Collection:
Department of Brain SciencesLaboratory of Neurodegenerative Diseases and Aging1. Journal Articles
Department of New BiologySenescence-Associated Mechanism Lab1. Journal Articles


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