Telomeres and telomerase represent, at least in theory, an extremely attractive target for cancer therapy. The objective of this review is to present the latest view on the mechanism(s) of action of telomerase inhibitors, with an emphasis on a specific class of telomere ligands called G-quadruplex ligands, and to discuss their potential use in oncology.
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http://dx.doi.org/10.1016/j.biochi.2007.07.011 | DOI Listing |
Sci Adv
January 2025
Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, Louisiana Cancer Research Center, 1700 Tulane Avenue, New Orleans, LA 70112, USA.
Unlike most species that use telomerase for telomere maintenance, many dipterans, including , rely on three telomere-specific retrotransposons (TRs)-, , and -to form tandem repeats at chromosome ends. Although TR transcription is crucial in their life cycle, its regulation remains poorly understood. This study identifies the Mediator complex, E2F1-Dp, and Scalloped/dTEAD as key regulators of TR transcription.
View Article and Find Full Text PDFClin Mol Hepatol
January 2025
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Background/aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC.
Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data.
FEBS Lett
January 2025
Dipartimento di Scienze, Università degli Studi "Roma Tre", Italy.
Some tumors employ a mechanism called alternative lengthening of telomeres (ALT) to counteract telomere shortening-induced replicative senescence. Several hallmarks are used to identify cell lines and tumors as ALT-positive. Here, we analyzed a panel of ALT-positive and -negative cancer cell lines to investigate the specificity and sensibility of ALT-associated markers.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Psychiatry and Behavioral Sciences and Weill Center for Neurosciences, University of California, San Francisco, CA, 94107, USA.
Telomere attrition is a hallmark of biological aging, contributing to cellular replicative senescence. However, few studies have examined the determinants of telomere attrition in vivo in humans. Mitochondrial Health Index (MHI), a composite marker integrating mitochondrial energy-transformation capacity and content, may be one important mediator of telomere attrition, as it could impact telomerase activity, a direct regulator of telomere maintenance.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
December 2024
Department of Obstetrics and Gynecology, Hefei Maternal and Child Health Hospital, Hefei, China.
Objective: Gestational diabetes mellitus (GDM) is a common complication during pregnancy and increases the risk of metabolic diseases in offspring. We hypothesize that the poor intrauterine environment in pregnant women with GDM may lead to chromosomal DNA damage and telomere damage in umbilical cord blood cells, providing evidence of an association between intrauterine programming and increased long-term metabolic disease risk in offspring.
Methods: We measured telomere length (TL), serum telomerase (TE) activity, and oxidative stress markers in umbilical cord blood mononuclear cells (CBMCs) from pregnant women with GDM (N=200) and healthy controls (Ctrls) (N=200) and analysed the associations of TL with demographic characteristics, biochemical indicators, and blood glucose levels.
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