Role of POT1 in Human Cancer

Wu, Ya-Na; Poulos, Rebecca C.; Reddel, Roger R.

doi:10.3390/cancers12102739

Cited by 40 publications

(38 citation statements)

References 147 publications

(206 reference statements)

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“…Lastly, POT1 is involved in telomere maintenance, and its regular activity results in cell aging and apoptosis. Three percent of malignancies have POT1 mutations; however, its prevalence is higher in AS (23%) and is described among the top predisposition genes for familial melanoma and cardiac AS [ 37 ]. In our cohort, it was predominately present in cases of H/N-AS.…”

Section: Discussionmentioning

confidence: 99%

Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis

Espejo-Freire

Elliott

Rosenberg

et al. 2021

Cancers

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We performed a retrospective analysis of angiosarcoma (AS) genomic biomarkers and their associations with the site of origin in a cohort of 143 cases. Primary sites were head and neck (31%), breast (22%), extremity (11%), viscera (20%), skin at other locations (8%), and unknown (9%). All cases had Next Generation Sequencing (NGS) data with a 592 gene panel, and 53 cases had Whole Exome Sequencing (WES) data, which we used to study the microenvironment phenotype. The immunotherapy (IO) response biomarkers Tumor Mutation Burden (TMB), Microsatellite Instability (MSI), and PD-L1 status were the most frequently encountered alteration, present in 36.4% of the cohort and 65% of head and neck AS (H/N-AS) (p < 0.0001). In H/N-AS, TMB-High was seen in 63.4% of cases (p < 0.0001) and PDL-1 positivity in 33% of cases. The most common genetic alterations were TP53 (29%), MYC amplification (23%), ARID1A (17%), POT1 (16%), and ATRX (13%). H/N-AS cases had predominantly mutations in TP53 (50.0%, p = 0.0004), POT1 (40.5%, p < 0.0001), and ARID1A (33.3%, p = 0.5875). In breast AS, leading alterations were MYC amplification (63.3%, p < 0.0001), HRAS (16.1%, p = 0.0377), and PIK3CA (16.1%, p = 0.2352). At other sites, conclusions are difficult to generate due to the small number of cases. A microenvironment with a high immune signature, previously associated with IO response, was evenly distributed in 13% of the cases at different primary sites. Our findings can facilitate the design and optimization of therapeutic strategies for AS.

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Section: Discussionmentioning

confidence: 99%

Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis

Espejo-Freire

Elliott

Rosenberg

et al. 2021

Cancers

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“…Finally, Microphthalmia-associated transcription factor (MITF) functions to regulate the expression of a collection of genes that play an important role in melanocyte proliferation and invasion, and a substitution mutation in the MITF gene results in a fivefold greater risk of developing melanoma, renal cancer, or both [ 14 ]. For detailed descriptions of the molecular roles of TERT, POT1, PTEN, and MITF, we encourage readers to consult the recent reviews aimed at exploring the function and disfunction of each gene [ 15 , 16 , 17 , 18 ].…”

Section: Heritable Etiologies For Melanoma Developmentmentioning

confidence: 99%

Etiologies of Melanoma Development and Prevention Measures: A Review of the Current Evidence

Djavid

Stonesifer

Fullerton

et al. 2021

Cancers

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(1) Melanoma is the most aggressive dermatologic malignancy, with an estimated 106,110 new cases to be diagnosed in 2021. The annual incidence rates continue to climb, which underscores the critical importance of improving the methods to prevent this disease. The interventions to assist with melanoma prevention vary and typically include measures such as UV avoidance and the use of protective clothing, sunscreen, and other chemopreventive agents. However, the evidence is mixed surrounding the use of these and other interventions. This review discusses the heritable etiologies underlying melanoma development before delving into the data surrounding the preventive methods highlighted above. (2) A comprehensive literature review was performed to identify the clinical trials, observational studies, and meta-analyses pertinent to melanoma prevention and incidence. Online resources were queried to identify epidemiologic and clinical trial information. (3) Evidence exists to support population-wide screening programs, the proper use of sunscreen, and community-targeted measures in the prevention of melanoma. Clinical evidence for the majority of the proposed preventive chemotherapeutics is presently minimal but continues to evolve. (4) Further study of these chemotherapeutics, as well as improvement of techniques in artificial intelligence and imaging techniques for melanoma screening, is warranted for continued improvement of melanoma prevention.

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“…As the telomeric single‐stranded DNA‐binding protein of shelterin, protection of telomere 1 (POT1) has been implicated in the DNA damage response, aging, and tumorigenesis (T. Li et al, 2020). It directly binds to single‐stranded telomeric DNA, protects chromosomal ends from DNA damage response, and plays a role in telomere length regulation (Wu et al, 2020). POT1 proteins in various organisms bind telomeres and regulate their structure and function (Yang et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐340‐5p increases telomere length by targeting telomere protein POT1 to improve Alzheimer's disease in mice

Zhang

Yang

et al. 2021

Cell Biology International

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Alzheimer′s disease (AD) is a chronic neurodegenerative disorder which is the primary cause of dementia in the elderly. Telomere attrition has been proposed as a hallmark of aging. Our study aimed to explore the mechanism of the protection of telomere 1 (POT1) in regulating telomere length and affecting cellular senescence in AD. The AD mouse model was established by d‐galactose and aluminum chloride, and the water maze test and dark avoidance test were used to detect the behaviors of mice and confirm the success of AD mouse model. AD cell model was established with HT22 cells induced by Aβ42 oligomers. POT1 expression in the AD model was detected by quantitative real‐time polymerase chain reaction. Cellular telomere length in hippocampal tissue was analyzed by telomere restriction fragment. Localization of intracellular POT1, telomerase, and telomeres was analyzed by immunofluorescence and fluorescence in situ hybridization. Dual‐luciferase assay was used to validate the targeted binding relationship between microRNA‐340‐5p (miR‐340‐5p) and POT1. After inhibiting POT1 expression, the symptoms of AD in mice were improved. Aβ1–42 deposition was reduced, whereas telomere length and telomerase activity was increased. Dual‐luciferase assay verified the binding relationship between miR‐340‐5p and POT1. An increase in miR‐340‐5p expression could alleviate cellular senescence and AD symptoms. miR‐340‐5p increased cellular telomere length and delayed cell senescence by inhibiting POT1 expression to improve AD symptoms. This study made a conclusion that miR‐340‐5p increased cellular telomere length and delayed cell senescence by inhibiting POT1 expression to improve AD symptoms in mice.

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Role of POT1 in Human Cancer

Cited by 40 publications

References 147 publications

Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis

Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis

Etiologies of Melanoma Development and Prevention Measures: A Review of the Current Evidence

MicroRNA‐340‐5p increases telomere length by targeting telomere protein POT1 to improve Alzheimer's disease in mice

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