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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.8
- 수록면
- 1 - 9 (9page)
- DOI
- 10.1038/s12276-020-00490-x
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초록· 키워드
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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.
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