Interestingly, the functional miR-128 binding site in TERT mRNA, is conserved between TERT and the other cellular reverse transcriptase encoded by Long Interspersed Elements-1 (LINE-1 or L1), which can also contribute to the oncogenic phenotype of cancer.
In contrast, cancer stem cells (CSCs) have short telomeres despite high expression of hTERT, indicating that the role of hTERT in CSCs is not limited to telomere elongation and/or maintenance.
Pooled analysis demonstrated that the TERT variant rs2736098 G > A polymorphism was significantly correlated with cancer risk in all populations (A vs. G: OR = 1.134, 95% CI = 1.051-1.224, <i>P</i> = 0.001; AA vs. GG: OR = 1.280, 95% CI = 1.087-1.508, <i>P</i> = 0.003; GA vs. GG: OR = 1.125, 95% CI = 1.020-1.240, <i>P</i> = 0.018; GA/AA vs. GG: OR = 1.159, 95% CI = 1.047-1.283, <i>P</i> = 0.004).
A systematic search of studies on the association of TERTrs2853669 polymorphism with all types of cancer was conducted in PubMed, Embase and Cochrane Library.
High-throughput genomic sequencing has identified alterations in the gene encoding human telomerase reverse transcriptase (TERT) as points of interest for elucidating the oncogenic mechanism of multiple different cancer types, including gliomas.
TERT catalyzes telomere maintenance.While silenced in most normal somatic cells, TERT is expressed in cancer, often due to promoter mutations, facilitating replicative immortality.
The TERTrs2736100 polymorphism was associated with increased overall cancer risk in five genetic models [homozygous model (GG vs. TT): odds ratio (OR) = 1.39, 95% confidence interval (95% CI) = 1.26-1.54, P < 0.001; heterozygous model (TG vs. TT): OR = 1.16, 95% CI = 1.11-1.23, P < 0.001; dominant model (TG + GG vs. TT): OR = 1.23, 95% CI = 1.15-1.31, P < 0.001; recessive model (GG vs. TG + TT): OR = 1.25, 95% CI = 1.16-1.35, P < 0.001; and allele contrast model (G vs. T): OR = 1.17, 95% CI = 1.12-1.23, P < 0.001].
Thus, our data will help to decipher the interaction networks of TERT and reveal the unknown functions of telomerase in cancer and aging-related diseases.
However, the majority of studies were conducted on cells that generally express high levels of TERT (cancer and immortalized cells) while the role of telomerase in CS in normal cells has been investigated to a much lesser extent.
In this study, we investigated a role of cell-cell contact-related molecules (protein ECM components, proteoglycans (PGs) and junction-related molecules) in intercellular communications between the human TERT immortalized fibroblasts (BjTERT fibroblasts) and normal (PNT2) or cancer (LNCaP, PC3, DU145) prostate epithelial cells.
It is established that induction of the telomerase reverse transcriptase gene (<i>TERT</i>) coupled with telomerase activation is essential for cancer development/progression and aberrant <i>TERT</i> promoter methylation of specific 5'-C-phosphate-G-3' (CpGs) has been linked to <i>TERT</i> induction in oncogenesis.
Mutations in the promoter region of telomerase reverse transcriptase (TERT) and alterations in telomere length (TL) have been the focus of research in various types of cancer.
Telomerase-specific replication-competent adenoviruses (Ads), i.e., TRADs, which possess an E1 gene expression cassette driven by the human telomerase reverse transcriptase promoter, are promising agents for cancer treatment.
A particular attention is given to the putative connections between TERT transcriptional reactivation and signalling pathways frequently altered in cancer, such as c-MYC, NF-κB and B-Catenin.
The recent findings of highly recurrent activating mutations in the promoter for the telomerase reverse transcriptase (TERT) gene in diverse human cancers, together with the widespread mutations in p53 in cancer, provide support for the idea that circumvention of a telomere-p53 checkpoint is essential for malignant progression in human cancer.
PTs significantly more frequently displayed mutations affecting MED12, the TERT gene promoter and bona fide cancer genes, whereas adenosarcomas harbored a higher rate of MDM2/CDK4 and TERT gene amplifications.
RrA could inhibit telomerase activity in SCOV-3, SkBr-3 and A549 human cancer cell lines due to its ability to down-regulate the expression of telomerase catalytic subunit hTERT.
Aberrant CpG dinucleotide methylation in a specific region of the telomerase reverse transcriptase (TERT) promoter is associated with increased TERT mRNA levels and malignancy in several cancer types.
Telomerase and TERT are expressed in cancer cells at every stage of tumour evolution, from the cancer stem cell to circulating tumour cells and tumour metastases.