PNAS: Why are older people more susceptible to cancer?

As people grow older, people will gradually get older, and the risk of being threatened by diseases including cancer will increase accordingly
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Although it has been known that this phenomenon is related to the aging of the basic unit cells that constitute the structure and function of the human body, the specific mechanism of disease caused by aging is still unclear

Recently, researchers from the Japan Association for Cancer Research and Genetics published a research report titled "Pericentromeric noncoding RNA changes DNA binding of CTCF and inflammatory gene expression in senescence and cancer" in the Proceedings of the National Academy of Sciences (PNAS) , Reveals how aging promotes cancer
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The report pointed out that the previous under-understood non-coding RNA in the centromere (ncRNA) of cell chromosomes may be the "main cause" of cancer.
With age, this type of RNA can promote the aging secretory phenotype (SASP).
The expression of inflammatory proteins promotes the occurrence of diseases
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This will provide new ideas for controlling "old age" diseases and helping people to better enjoy the life of old age

To find out the link between cellular senescence and disease, the researchers first compared the difference in gene expression of human embryonic lung fibroblasts (IMR-90) under normal proliferation and X-ray-induced senescence
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Transposase accessible chromatin sequencing (ATAC-seq) showed that the peak intensity of a total of 16,325 points changed significantly

By integrating these data with published data, the researchers "discovered" something unusual
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A type of ncRNA called "Human Satellite II" located in the centromere part of the cell chromosome exhibits genetic silencing in normal cells

Cell senescence can cause significant changes in its chromatin organization, and CCCTC-binding factor (CTCF) is involved in this process
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CTCF is a multifunctional transcription factor widely found in eukaryotes

To solve this mystery, the researchers identified 26 chromatin-binding proteins of hSATII RNA through gene ontology (GO) analysis, and focused on the RNA-binding protein CTCF
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RNA immunoprecipitation analysis showed that when CTCF is missing, the expression of sasp-like inflammatory genes caused by hSATII RNA is significantly up-regulated, and when the regulatory factor is overexpressed, the expression of sasp-like inflammatory genes is down-regulated

Previous studies have shown that human satellite RNA may induce chromosomal instability (CIN), which is one of the risk factors for the development of cancer
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Therefore, in further analysis, the researchers explored whether the interference of hSATII RNA on CTCF function can induce CIN, and found that cells overexpressing hSATII RNA showed obvious CIN characteristics and tumor cell phenotypes, while CTCF overexpression eliminated hSATII RNA-induced CIN suggests that hSATII may promote the occurrence of tumors as the cells age

In addition, the researchers also found that hSATII RNA in senescent cells can be transferred to surrounding normal cells through extracellular vesicles (EV), thereby promoting the expression of sasp-like inflammatory genes in other cells and the occurrence of CIN
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In summary, this report focuses on the role of hSATII RNA near the centromere in the occurrence and development of cancer with age
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Promote tumor development by regulating sasp-like inflammatory factors and ev metastasis