Conserved G-Quadruplex-Forming Sequences in Mammalian TERT Promoters and Their Effect on Mutation Frequency DOI Creative Commons

Vera V. Panova,

Nina G. Dolinnaya,

Kirill A. Novoselov

et al.

Life, Journal Year: 2023, Volume and Issue: 13(7), P. 1478 - 1478

Published: June 29, 2023

Somatic mutations in the promoter region of human telomerase reverse transcriptase (hTERT) gene have been identified many types cancer. The hTERT is known to be enriched with sequences that enable formation G-quadruplex (G4) structures, whose presence associated elevated mutagenicity and genome instability. Here, we used a bioinformatics tool (QGRS mapper) search for G4-forming (G4 motifs) 1000 bp TERT regions 141 mammalian species belonging 20 orders, 5 which, including primates predators, contain more than 10 species. Groups conserved G4 motifs single-nucleotide variants within these groups were discovered using block alignment approach (based on Nucleotide PanGenome explorer). It has shown that: (i) are predominantly located proximal transcription start site (up 400 bp) over-represented non-coding strand promoters, (ii) 11 22% found evolutionarily across related organisms, (iii) statistically significant higher frequency nucleotide substitutions compared surrounding was confirmed only order Primates. These data support assumption G4s can interfere DNA repair process affect evolutionary adaptation organisms

Language: Английский

Exploring the Link Between Telomeres and Mitochondria: Mechanisms and Implications in Different Cell Types DOI Open Access
Graziana Assalve, Paola Lunetti, Maria Santa Rocca

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 993 - 993

Published: Jan. 24, 2025

Telomeres protect chromosome ends from damage, but they shorten with each cell division due to the limitations of DNA replication and are further affected by oxidative stress. This shortening is a key feature aging, telomerase, an enzyme that extends telomeres, helps mitigate this process. Aging also associated mitochondrial dysfunction, leading increased reactive oxygen species (ROS) exacerbate cellular damage promote apoptosis. Elevated ROS levels can telomeres oxidizing guanine disrupting their regulation. Conversely, telomere impacts function, activation telomerase has been shown reverse decline. A critical link between dysfunction response, which activates tumor suppressor protein p53, resulting in reduced biogenesis metabolic disruptions. highlights bidirectional relationship maintenance function. review explores complex interactions mitochondria across various types, fibroblasts sperm cells, shedding light on interconnected mechanisms underlying aging

Language: Английский

Citations

1
The importance of protein domain mutations in cancer therapy DOI Creative Commons
Kiran Kumar Chitluri, Isaac Arnold Emerson

Heliyon, Journal Year: 2024, Volume and Issue: 10(6), P. e27655 - e27655

Published: March 1, 2024

Cancer is a complex disease that caused by multiple genetic factors. Researchers have been studying protein domain mutations to understand how they affect the progression and treatment of cancer. These can significantly impact development spread cancer changing structure, function, signalling pathways. As result, there growing interest in these be used as prognostic indicators for prognosis. Recent studies shown provide valuable information about severity patient's response treatment. They may also predict resistance targeted therapy The clinical implications are significant, regarded essential biomarkers oncology. However, additional techniques approaches required characterize changes domains their functional effects. Machine learning other computational tools offer promising solutions this challenge, enabling prediction on structure function. Such predictions aid interpretation information. Furthermore, genome editing like CRISPR/Cas9 has made it possible validate significance mutants more efficiently accurately. In conclusion, hold great promise predictive Overall, considerable research still needed better define molecular heterogeneity resolve challenges remain, so full potential realized.

Language: Английский

Citations

4
Development of 3D Cell-Based Fluorescent Reporter Assay for Screening of Drugs Downregulating Telomerase Reverse Transcriptase DOI Creative Commons
You Li, Fengli Zhang, Zhen Qin

et al.

Bioengineering, Journal Year: 2025, Volume and Issue: 12(4), P. 335 - 335

Published: March 23, 2025

A fluorescent cell-based assay was developed for the screening of chemicals repressing expression human telomerase reverse transcriptase (hTERT). hTERT is reactivated during carcinogenesis and overexpressed in more than 90% cancers but almost silent normal tissue cells. Because its critical role cancer, a target various therapeutic strategies cancer treatment. In this study, promoter cloned MCF7 breast cells used to control enhanced green protein (EGFP). The fluorescence EGFP indicated activity promoter, and, presence an repressor, signal reduced as compared controlled by cytomegalovirus (CMV) which not affected changes culture conditions worked control. reporter were cultivated three-dimensional (3D) microbioreactors resemble vivo tumor physiology provide vivo-like responses. assay’s predictability demonstrated with three known inhibitors, pristimerin, epigallocatechin gallate, n-butylidenephthalide, further evaluated five widely anticancer compounds, doxorubicin, cisplatin, paclitaxel, blasticidin, tamoxifen. results showed overall accuracy over 83.3%, demonstrating feasibility using potential drugs targeting hTERT.

Language: Английский

Citations

0
ACYP2 functions as an innovative nano-therapeutic target to impede the progression of hepatocellular carcinoma by inhibiting the activity of TERT and the KCNN4/ERK pathway DOI Creative Commons
Yixuan Wu,

Hongyi Bao,

Jinran Wu

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 12, 2024

An increasing body of evidence suggests that acylphosphatase-2 (ACYP2) polymorphisms are correlated with an increased susceptibility to a range malignancies. Nevertheless, its potential functions, molecular mechanisms in hepatocellular carcinoma (HCC) and whether it can be act as therapeutic target remain uninvestigated. Herein, ACYP2 was found lowly expressed HCC negatively tumor size, differentiation, microvascular invasion the prognosis patients. Functional investigations revealed overexpression inhibited proliferation metastasis cells while promoting apoptosis; knockdown had exact opposite effect. Additionally, observed distributed both cytoplasm nucleus cells. According mechanistic studies, expression potassium calcium-activated channel subfamily N member 4 (KCNN4) regulated by cytoplasmic ACYP2, resulting inhibition K

Language: Английский

Citations

2
Conserved G-Quadruplex-Forming Sequences in Mammalian TERT Promoters and Their Effect on Mutation Frequency DOI Creative Commons

Vera V. Panova,

Nina G. Dolinnaya,

Kirill A. Novoselov

et al.

Life, Journal Year: 2023, Volume and Issue: 13(7), P. 1478 - 1478

Published: June 29, 2023

Somatic mutations in the promoter region of human telomerase reverse transcriptase (hTERT) gene have been identified many types cancer. The hTERT is known to be enriched with sequences that enable formation G-quadruplex (G4) structures, whose presence associated elevated mutagenicity and genome instability. Here, we used a bioinformatics tool (QGRS mapper) search for G4-forming (G4 motifs) 1000 bp TERT regions 141 mammalian species belonging 20 orders, 5 which, including primates predators, contain more than 10 species. Groups conserved G4 motifs single-nucleotide variants within these groups were discovered using block alignment approach (based on Nucleotide PanGenome explorer). It has shown that: (i) are predominantly located proximal transcription start site (up 400 bp) over-represented non-coding strand promoters, (ii) 11 22% found evolutionarily across related organisms, (iii) statistically significant higher frequency nucleotide substitutions compared surrounding was confirmed only order Primates. These data support assumption G4s can interfere DNA repair process affect evolutionary adaptation organisms

Language: Английский

Citations

2