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Genomic and Transcriptomic Alterations in Cancer and Aging

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A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Genetics and Genomics".

Deadline for manuscript submissions: closed (15 July 2022) | Viewed by 13767

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Special Issue Editor

Dr. Anastasiya V. Snezhkina

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Guest Editor

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
Interests: molecular oncology; genomics; transcriptomics; epigenetics; energy metabolism; mutations; mutational load; oxidative stress

Special Issue Information

Dear Colleagues,

Сarcinogenesis is widely associated with genomic and transcriptomic alterations, including genetic mutations (base substitutions, insertions, deletions, and chromosomal rearrangements), copy number variations, changes in mRNA and noncoding RNA expression levels, and alternatively spliced variants. All these changes also occur during aging that, in turn, is a major risk factor for cancer development. In both cases, the key question is how genomic and transcriptomic alterations support cancer initiation and progression and what their contribution to aging is. The close interconnection of cancer and aging implies the possibly shared mechanisms underpinning the two processes. However, the causative relations are not straightforward, as these processes are fundamentally opposite in the context of cell biological functioning. A better understanding of cancer and aging biology will allow revealing the molecular connections that presently remain unclear.

Dr. Anastasiya Snezhkina
Guest Editor

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Keywords

Genomics
Transcriptomics
Cancer
Aging
Molecular connections

Published Papers (5 papers)

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Research

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13 pages, 1553 KiB

Open AccessArticle

Suppression of OCT-1 in Metastatic Breast Cancer Cells Reduces Tumor Metastatic Potential, Hypoxia Resistance, and Drug Resistance

by Alexander G. Stepchenko, Elizaveta V. Bulavkina, Tatiana N. Portseva, Sofia G. Georgieva and Elizaveta V. Pankratova

Life 2022, 12(9), 1435; https://doi.org/10.3390/life12091435 - 15 Sep 2022

Cited by 1 | Viewed by 1743

Abstract

OCT-1/POU2F1 is a ubiquitously expressed transcription factor. Its expression starts at the earliest stage of embryonic development. OCT-1 controls genes involved in the regulation of differentiation, proliferation, cell metabolism, and aging. High levels of OCT-1 transcription factor in tumor cells correlate with tumor malignancy and resistance to antitumor therapy. Here, we report that suppression of OCT-1 in breast cancer cells reduces their metastatic potential and drug resistance. OCT-1 knockdown in the MDA-MB231 breast cancer cells leads to a fivefold decrease (p < 0.01) in cell migration rates in the Boyden chamber. A decrease in the transcription levels of human invasion signature (HIS) genes (ARHGDIB, CAPZA2, PHACTR2, CDC42, XRCC5, and CAV1) has been also demonstrated by real-time PCR, with high expression of these genes being a hallmark of actively metastasizing breast cancer cells. Transcriptional activity of ATF6 response elements is significantly reduced in the cell lines with decreased OCT-1 expression, which results in lower levels of adaptive EPR stress response. OCT-1 knockdown more than two times increases the MDA-MB231 cell death rate in hypoxia and significantly increases the doxorubicin or docetaxel-treated MDA-MB231 cell death rate. Our findings indicate that OCT-1 may be an important therapeutic target and its selective inhibition may have significant therapeutic effects and may improve prognosis in breast cancer patients. Full article

(This article belongs to the Special Issue Genomic and Transcriptomic Alterations in Cancer and Aging)

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26 pages, 5141 KiB

Open AccessEditor’s ChoiceArticle

Clinical Relevance of Secreted Small Noncoding RNAs in an Embryo Implantation Potential Prediction at Morula and Blastocyst Development Stages

by Angelika V. Timofeeva, Ivan S. Fedorov, Maria A. Shamina, Vitaliy V. Chagovets, Nataliya P. Makarova, Elena A. Kalinina, Tatiana A. Nazarenko and Gennady T. Sukhikh

Life 2021, 11(12), 1328; https://doi.org/10.3390/life11121328 - 1 Dec 2021

Cited by 5 | Viewed by 2482

Abstract

Despite the improvements in biotechnological approaches and the selection of controlled ovarian hyperstimulation protocols, the resulting pregnancy rate from in vitro fertilization (IVF) protocols still does not exceed 30–40%. In this connection, there is an acute question of the development of a non-invasive, sensitive, and specific method for assessing the implantation potential of an embryo. A total of 110 subfertile couples were included in the study to undergo the IVF/ICSI program. Obtained embryos for transfer into the uterine cavity of patient cohort 1 (n = 60) and cohort 2 (n = 50) were excellent/good-quality blastocysts, and small noncoding RNA (sncRNA) content in the corresponding spent culture medium samples at the morula stage (n = 43) or at the blastocyst stage (n = 31) was analyzed by deep sequencing followed by qRT-PCR in real time. Two logistic regression models were developed to predict the implantation potential of the embryo with 100% sensitivity and 100% specificity: model 1 at the morula stage, using various combinations of hsa_piR_022258, hsa-let-7i-5p, hsa_piR_000765, hsa_piR_015249, hsa_piR_019122, and hsa_piR_008112, and model 2 at the blastocyst stage, using various combinations of hsa_piR_020497, hsa_piR_008113, hsa-miR-381-3p, hsa_piR_022258, and hsa-let-7a-5p. Protein products of sncRNA potential target genes participate in the selective turnover of proteins through the ubiquitination system and in the organization of the various cell cytoskeleton and nucleoskeleton structures, regulating the activity of the Hippo signaling pathway, which determines the fate specification of the blastomers. Full article

(This article belongs to the Special Issue Genomic and Transcriptomic Alterations in Cancer and Aging)

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24 pages, 10493 KiB

Open AccessArticle

Clusterin and Its Potential Regulatory microRNAs as a Part of Secretome for the Diagnosis of Abnormally Invasive Placenta: Accreta, Increta, and Percreta Cases

by Angelika V. Timofeeva, Ivan S. Fedorov, Mariya M. Pirogova, Oksana N. Vasilchenko, Vitaliy V. Chagovets, Larisa S. Ezhova, Tatiana M. Zabelina, Roman G. Shmakov and Gennadiy T. Sukhikh

Life 2021, 11(4), 270; https://doi.org/10.3390/life11040270 - 24 Mar 2021

Cited by 8 | Viewed by 2401

Abstract

Magnetic resonance imaging (MRI) and ultrasound methods used for the diagnosis of an abnormally invasive placenta (AIP) have a wide range of sensitivity (Se, 33–93%) and specificity (Sp, 71–100%) levels, which results in a high risk of unfavorable maternal and perinatal outcomes. The relevance of optimizing the diagnosis of AIP is beyond doubt. Given the epigenetic nature of trophoblast invasion, we aimed to quantitate microRNAs and proteins of their target genes that are potentially associated with AIP in blood plasma samples from 64 pregnant women at gestation weeks 30–34 by reverse transcription coupled with polymerase chain reaction (RT-PCR) and Western blotting, respectively. Statistically significant increases in the expression levels of hsa-miR-17-5p, hsa-miR-21-5p, hsa-miR-25-3p, hsa-miR-92a-3p, and hsa-miR-320a-3p were revealed in the groups of women with AIP (accreta, increta, percreta) relative to the group of women with scars on the uterus or to the group with placenta previa. Opposite changes in the expression level of “gene–target protein/miRNA” pairs were found for the α-subunit of the clusterin secretory form and any of the hsa-miR-21-5p, hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-320a-3p, and hsa-miR-17-5p in all cases of AIP. The developed logistic regression models to diagnose AIP cases of various severity gave Se values of 88.8–100% and Sp values of 91.6–100% using a combination of hsa-miR-21-5p, hsa-miR-92a-3p, hsa-miR-320a-3p, or clusterin levels. Full article

(This article belongs to the Special Issue Genomic and Transcriptomic Alterations in Cancer and Aging)

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15 pages, 2291 KiB

Open AccessArticle

De Novo Transcriptome Profiling of Brain Tissue from the Annual Killifish Nothobranchius guentheri

by Zulfiia G. Guvatova, Maria S. Fedorova, Yulia S. Vershinina, Elena A. Pudova, Anastasiya V. Lipatova, Vsevolod V. Volodin, Natalya S. Gladysh, Artemiy T. Tokarev, Alexey B. Kornev, Vladislav S. Pavlov, Ildar R. Bakhtogarimov, Evgeny Y. Krysanov, Alexey A. Moskalev, George S. Krasnov and Anna V. Kudryavtseva

Life 2021, 11(2), 137; https://doi.org/10.3390/life11020137 - 11 Feb 2021

Cited by 5 | Viewed by 3208

Abstract

Nothobranchius is a genus of small annual killifish found in Africa. Due to the relatively short lifespan, as well as easy breeding and care, Nothobranchius fish are becoming widely used as a vertebrate model system. Studying the genome and transcriptome of these fish is essential for advancing the field. In this study, we performed de novo transcriptome assembly of brain tissues from Nothobranchius guentheri using Trinity. Annotation of 104,271 potential genes (with transcripts longer than 500 bp) was carried out; for 24,967 genes (53,654 transcripts), in which at least one GO annotation was derived. We also analyzed the effect of a long-term food supplement with Torin 2, second-generation ATP-competitive inhibitor of mTOR, on the gene expression changes in brain tissue of adult N. guentheri. Overall, 1491 genes in females and 249 genes in males were differently expressed under Torin 2-supplemented diet. According to the Gene Set Enrichment Analysis (GSEA), the majority of identified genes were predominantly involved in the regulation of metabolic process, dendritic spine maintenance, circadian rhythms, retrotransposition, and immune response. Thus, we have provided the first transcriptome assembly and assessed the differential gene expression in response to exposure to Torin 2, which allow a better understanding of molecular changes in the brain tissues of adult fish in the mTOR pathway inhibition. Full article

(This article belongs to the Special Issue Genomic and Transcriptomic Alterations in Cancer and Aging)

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Review

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22 pages, 868 KiB

Open AccessReview

Potential Biomarkers of Metastasizing Paragangliomas and Pheochromocytomas

by Anastasiya Snezhkina, Vladislav Pavlov, Alexey Dmitriev, Nataliya Melnikova and Anna Kudryavtseva

Life 2021, 11(11), 1179; https://doi.org/10.3390/life11111179 - 4 Nov 2021

Cited by 7 | Viewed by 2681

Abstract

Paragangliomas and pheochromocytomas (PPGLs) are rare neuroendocrine tumors originating from paraganglionic tissue in many sites of the body. Most PPGLs are characterized by nonaggressive behavior but all of them have the potential to metastasize. PPGLs represent a great diagnostic dilemma as it is difficult to recognize tumors that are likely to be metastasizing; criteria of malignancy can be found both in benign and metastatic forms. This review aims to analyze the current knowledge of the nature of metastasizing PPGLs paying particular attention to head and neck paragangliomas (HNPGLs). Potential predictors of the malignancy risk for PPGLs were summarized and discussed. These data may also help in the development of diagnostic and prognostic strategies, as well as in the identification of novel potential therapeutic targets for patients with PPGLs. Full article

(This article belongs to the Special Issue Genomic and Transcriptomic Alterations in Cancer and Aging)

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