Integration of Telomere Length Dynamics into Systems Biology Framework: A Review

Nersisyan, Lilit

doi:10.4137/grsb.s39836

Cited by 2 publications

(2 citation statements)

References 86 publications

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“…DNA-seq data were taken from patient matched pairs of s-CRC tumors and normal mucosa (5 MSS cases and 8 MSI cases). RNA-seq data refer to unmatched cases of reference mucosa (20 samples), MSS s-CRC (21), MSI-low s-CRC (24), and MSI-high s-CRC (20). In accordance with previous studies (47) the MSS and MSI-low samples were subsumed into one combined MSS group.…”

Section: Methodsmentioning

confidence: 99%

Telomere Length Maintenance and Its Transcriptional Regulation in Lynch Syndrome and Sporadic Colorectal Carcinoma

et al. 2019

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Background: Activation of telomere maintenance mechanisms (TMMs) is a hallmark of most cancers, and is required to prevent genome instability and to establish cellular immortality through reconstitution of capping of chromosome ends. TMM depends on the cancer type. Comparative studies linking tumor biology and TMM have potential impact for evaluating cancer onset and development.Methods: We have studied alterations of telomere length, their sequence composition and transcriptional regulation in mismatch repair deficient colorectal cancers arising in Lynch syndrome (LS-CRC) and microsatellite instable (MSI) sporadic CRC (MSI s-CRC), and for comparison, in microsatellite stable (MSS) s-CRC and in benign colon mucosa. Our study applied bioinformatics analysis of whole genome DNA and RNA sequencing data and a pathway model to study telomere length alterations and the potential effect of the “classical” telomerase (TEL-) and alternative (ALT-) TMM using transcriptomic signatures.Results: We have found progressive decrease of mean telomere length in all cancer subtypes compared with reference systems. Our results support the view that telomere attrition is an early event in tumorigenesis. TMM gets activated in all tumors studied due to concerted overexpression of a large fraction of genes with direct relation to telomere function, where only a very small fraction of them showed recurrent mutations. TEL-related transcriptional state was dominating in all CRC subtypes, showing, however, subtype-specific activation patterns; while contribution of the ALT-TMM was slightly more prominent in the hypermutated MSI s-CRC and LS-CRC. TEL-TMM is mainly activated by over-expression of DKC1 and/or TERT genes and their interaction partners, where DKC1 is more prominent in MSS than in MSI s-CRC and can serve as a transcriptomic marker of TMM activity.Conclusions: Our results suggest that transcriptional patterns are indicative for TMM pathway activation with subtle differences between TEL and ALT mechanisms in a CRC subtype-specific fashion. Sequencing data potentially provide a suited measure to study alterations of telomere length and of underlying transcriptional regulation. Further studies are needed to improve this method.

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Section: Methodsmentioning

confidence: 99%

Telomere Length Maintenance and Its Transcriptional Regulation in Lynch Syndrome and Sporadic Colorectal Carcinoma

et al. 2019

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“…[ 79 ]. Thus, it is always considered as an indicator for cellular senescence [ 80 - 82 ]. Telomere length was negatively correlated with aging in the Bama population [ 83 ].…”

Section: Genetic Factorsmentioning

confidence: 99%

Which Factors Influence Healthy Aging? A Lesson from the Longevity Village of Bama in China

Zhang¹,

Huang²,

Kang³

et al. 2023

Aging and disease

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A growing aging population is associated with increasing incidences of aging-related diseases and socioeconomic burdens. Hence, research into healthy longevity and aging is urgently needed. Longevity is an important phenomenon in healthy aging. The present review summarizes the characteristics of longevity in the elderly population in Bama, China, where the proportion of centenarians is 5.7-fold greater than the international standard. We examined the impact of genetic and environmental factors on longevity from multiple perspectives. We proposed that the phenomenon of longevity in this region is of high value for future investigations in healthy aging and aging-related disease and may provide guidance for fostering the establishment and maintenance of a healthy aging society.

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Integration of Telomere Length Dynamics into Systems Biology Framework: A Review

Cited by 2 publications

References 86 publications

Telomere Length Maintenance and Its Transcriptional Regulation in Lynch Syndrome and Sporadic Colorectal Carcinoma

Telomere Length Maintenance and Its Transcriptional Regulation in Lynch Syndrome and Sporadic Colorectal Carcinoma

Which Factors Influence Healthy Aging? A Lesson from the Longevity Village of Bama in China

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