scholarly journals Aberrant mitochondrial function in ageing and cancer

2019 ◽  
Vol 21 (4) ◽  
pp. 445-459 ◽  
Author(s):  
Julia C. Whitehall ◽  
Laura C. Greaves
Keyword(s):  
Risk Factor ◽  
Cancer Cells ◽  
Tumour Growth ◽  
Somatic Mutations ◽  
Mitochondrial Metabolism ◽  
Cancer Development ◽  
Mtdna Mutations ◽  
Age Related ◽  
Mitochondrial Functions ◽  
Cancer Types

AbstractAlterations in mitochondrial metabolism have been described as one of the major hallmarks of both ageing cells and cancer. Age is the biggest risk factor for the development of a significant number of cancer types and this therefore raises the question of whether there is a link between age-related mitochondrial dysfunction and the advantageous changes in mitochondrial metabolism prevalent in cancer cells. A common underlying feature of both ageing and cancer cells is the presence of somatic mutations of the mitochondrial genome (mtDNA) which we postulate may drive compensatory alterations in mitochondrial metabolism that are advantageous for tumour growth. In this review, we discuss basic mitochondrial functions, mechanisms of mtDNA mutagenesis and their metabolic consequences, and review the evidence for and against a role for mtDNA mutations in cancer development.

scholarly journals Mutant TP53 disrupts age-related accumulation patterns of somatic mutations in multiple cancer types

2016 ◽  
Vol 209 (9) ◽  
pp. 376-380 ◽  
Author(s):  
Wensheng Zhang ◽  
Erik K. Flemington ◽  
Kun Zhang
Keyword(s):  
Somatic Mutations ◽  
Multiple Cancer ◽  
Age Related ◽  
Cancer Types

scholarly journals Age-Associated Epigenetic Alterations, Somatic Mutations, and Their Crosstalk in Alzheimer’s Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 636-637
Author(s):  
Yaroslav Markov ◽  
Kyra Thrush ◽  
Morgan Levine
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Somatic Mutations ◽  
Brain Regions ◽  
Major Risk Factor ◽  
Postmortem Brain ◽  
Biological Aging ◽  
Learning Approaches ◽  
Age Related

Abstract Aging is the major risk factor for Alzheimer’s Disease (AD), and as life expectancy increases, neurodegeneration will continue to afflict an ever-increasing proportion of the population. While numerous theories are attempting to explain the drivers behind AD pathology, what unites them is the observation that AD is reliably associated with a progressive buildup of age-related molecular changes. Because of the varying clinical presentations of AD in patients with similar genetic backgrounds, it has been postulated that epigenetics may be implicated in its etiology. Building on our prior work showing that AD pathology is linked to alterations in age-related DNA CpG methylation (DNAme) across various brain regions, we use state-of-the-art machine learning approaches to identify patterns of molecular damage in postmortem brain samples. We show that alterations in DNAme are associated with accelerated biological aging, AD, and the APOE e4 genotype, which is a major risk factor for AD. We also demonstrate that these associations are present in the PFC but not cerebellum -- in line with the current understanding of AD progression in the brain. Finally, we perform whole-exome sequencing and protein mass spectrometry on the same brain samples to test our hypothesis as to whether AD-associated alterations of DNAme are linked with the accumulation of somatic mutations that affect the structural and binding properties of protein epigenetic regulators.

scholarly journals A truncating mutation in the autophagy gene UVRAG drives inflammation and tumorigenesis in mice

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Christine Quach ◽  
Ying Song ◽  
Hongrui Guo ◽  
Shun Li ◽  
Hadi Maazi ◽  
...  
Keyword(s):  
Risk Factor ◽  
Genetic Basis ◽  
Inflammatory Diseases ◽  
Cancer Development ◽  
Truncating Mutation ◽  
Autophagy Gene ◽  
Age Related ◽  
Underlying Mechanisms

AbstractAberrant autophagy is a major risk factor for inflammatory diseases and cancer. However, the genetic basis and underlying mechanisms are less established. UVRAG is a tumor suppressor candidate involved in autophagy, which is truncated in cancers by a frameshift (FS) mutation and expressed as a shortened UVRAGFS. To investigate the role of UVRAGFS in vivo, we generated mutant mice that inducibly express UVRAGFS (iUVRAGFS). These mice are normal in basal autophagy but deficient in starvation- and LPS-induced autophagy by disruption of the UVRAG-autophagy complex. iUVRAGFS mice display increased inflammatory response in sepsis, intestinal colitis, and colitis-associated cancer development through NLRP3-inflammasome hyperactivation. Moreover, iUVRAGFS mice show enhanced spontaneous tumorigenesis related to age-related autophagy suppression, resultant β-catenin stabilization, and centrosome amplification. Thus, UVRAG is a crucial autophagy regulator in vivo, and autophagy promotion may help prevent/treat inflammatory disease and cancer in susceptible individuals.

scholarly journals Disruption of ubiquitin mediated proteolysis is a widespread mechanism of tumorigenesis

2018 ◽  
Author(s):  
Francisco Martinez-Jimenez ◽  
Ferran Muinos ◽  
Erika Lopez-Arribillaga ◽  
Nuria Lopez-Bigas ◽  
Abel Gonzalez-Perez
Keyword(s):  
Random Forest ◽  
Positive Selection ◽  
Somatic Mutations ◽  
Random Forest Classifier ◽  
Human Proteome ◽  
Cancer Development ◽  
Driver Mutations ◽  
Primary Tumors ◽  
E3 Ligases ◽  
Cancer Types

E3 ligases and degrons --the sequences they recognize in target proteins-- are key parts of the ubiquitin-mediated proteolysis system. There are several examples of alterations of these two components of the system that play a role in cancer. Here, we uncovered the landscape of the contribution of such alterations to tumorigenesis across cancer types. We first systematically identified novel instances of degrons across the human proteome using a random forest classifier, and validated them exploiting somatic mutations across more than 7,000 tumors. We detected signals of positive selection across these novel degrons and revealed new instances involved in cancer development. Overall, we estimated that at least one in seven driver mutations across primary tumors affect either degrons or E3 ligases.

scholarly journals Apelin Effects Migration and Invasion Abilities of Colon Cancer Cells

Cells ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 113 ◽  
Author(s):  
Marta Podgórska ◽  
Katarzyna Pietraszek-Gremplewicz ◽  
Dorota Nowak
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Development ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Cellular Processes ◽  
Anti Cancer ◽  
Cancer Types ◽  
Membrane Type

Colon cancer is one of the most common cancer types. Its positive correlation with general obesity has led to increasing amounts of research focusing on the role of adipokines in colon cancer development. Apelin is a peptide released by adipose tissue that could affect many cellular processes connected with carcinogenesis. In this study, we examined the role of apelin in the motility regulation of colon cancer cells. We showed that the effect of four different apelin peptides increased the ability of cancer cells to migrate and invade examined cells trough influencing migratory protrusions formation and actin cytoskeleton rearrangement. Additionally, using confocal microscopy, we noticed that apelin stimulated the proteolytic activity of cancer cells, especially increasing the level of membrane-type 1 matrix metalloprotease. Taken together, apelin increased the movement of colon cancer cells through several possible mechanisms. Moreover, better understanding the process through which apelin regulates cancer development is still necessary to the creation of novel anti-cancer therapy.

scholarly journals The Complicated Nature of Somatic mtDNA Mutations in Aging

2022 ◽  
Vol 2 ◽  
Author(s):  
Monica Sanchez-Contreras ◽  
Scott R. Kennedy
Keyword(s):  
Energy Production ◽  
Somatic Mutations ◽  
De Novo ◽  
The Elderly ◽  
Exact Role ◽  
Mtdna Mutations ◽  
Age Related ◽  
Transport Chain ◽  
Considerable Debate ◽  
Complicated Nature

Mitochondria are the main source of energy used to maintain cellular homeostasis. This aspect of mitochondrial biology underlies their putative role in age-associated tissue dysfunction. Proper functioning of the electron transport chain (ETC), which is partially encoded by the extra-nuclear mitochondrial genome (mtDNA), is key to maintaining this energy production. The acquisition of de novo somatic mutations that interrupt the function of the ETC have long been associated with aging and common diseases of the elderly. Yet, despite over 30 years of study, the exact role(s) mtDNA mutations play in driving aging and its associated pathologies remains under considerable debate. Furthermore, even fundamental aspects of age-related mtDNA mutagenesis, such as when mutations arise during aging, where and how often they occur across tissues, and the specific mechanisms that give rise to them, remain poorly understood. In this review, we address the current understanding of the somatic mtDNA mutations, with an emphasis of when, where, and how these mutations arise during aging. Additionally, we highlight current limitations in our knowledge and critically evaluate the controversies stemming from these limitations. Lastly, we highlight new and emerging technologies that offer potential ways forward in increasing our understanding of somatic mtDNA mutagenesis in the aging process.

scholarly journals Extensive tissue-related and allele-related mtDNA heteroplasmy suggests positive selection for somatic mutations

2015 ◽  
Vol 112 (8) ◽  
pp. 2491-2496 ◽  
Author(s):  
Mingkun Li ◽  
Roland Schröder ◽  
Shengyu Ni ◽  
Burkhard Madea ◽  
Mark Stoneking
Keyword(s):  
Positive Selection ◽  
Protein Function ◽  
Somatic Mutations ◽  
Significant Excess ◽  
High Frequencies ◽  
Mtdna Mutations ◽  
Age Related ◽  
Selection For ◽  
Different Tissues ◽  
Complete Mtdna

Heteroplasmy in human mtDNA may play a role in cancer, other diseases, and aging, but patterns of heteroplasmy variation across different tissues have not been thoroughly investigated. Here, we analyzed complete mtDNA genome sequences at ∼3,500× average coverage from each of 12 tissues obtained at autopsy from each of 152 individuals. We identified 4,577 heteroplasmies (with an alternative allele frequency of at least 0.5%) at 393 positions across the mtDNA genome. Surprisingly, different nucleotide positions (nps) exhibit high frequencies of heteroplasmy in different tissues, and, moreover, heteroplasmy is strongly dependent on the specific consensus allele at an np. All of these tissue-related and allele-related heteroplasmies show a significant age-related accumulation, suggesting positive selection for specific alleles at specific positions in specific tissues. We also find a highly significant excess of liver-specific heteroplasmies involving nonsynonymous changes, most of which are predicted to have an impact on protein function. This apparent positive selection for reduced mitochondrial function in the liver may reflect selection to decrease damaging byproducts of liver mitochondrial metabolism (i.e., “survival of the slowest”). Overall, our results provide compelling evidence for positive selection acting on some somatic mtDNA mutations.

Milk fermented by Lactobacillus casei CRL431 modifies cytokine profiles associated to different stages of breast cancer development in mice

2019 ◽  
Vol 10 (6) ◽  
pp. 689-697 ◽  
Author(s):  
V.E. Méndez Utz ◽  
G. Perdigón ◽  
A. de Moreno de LeBlanc
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Inflammatory Response ◽  
Cancer Cells ◽  
Lactobacillus Casei ◽  
Tumour Growth ◽  
Fermented Milk ◽  
Interleukin 10 ◽  
Cancer Development

Breast cancer is one of the leading causes of death worldwide. It is recognised that immune system influences its promotion, progression, and metastasis, as well as their responsiveness to therapies. Previously, it was reported that milk fermented by Lactobacillus casei CRL431 decreased tumour growth and metastasis in a mouse breast cancer model, through the modulation of the host immune response. The aim of the present work was to analyse the systemic immune response induced by the administration of probiotic fermented milk (PFM) at different stages of cancer development, evaluating cytokines produced by splenocytes stimulated in vitro with 4T1 tumour cells, or its conditioned medium (CM). Groups of healthy mice and mice bearing 4T1 tumour or suffering metastasis after tumour surgery were studied. Results showed that at the early stages, PFM maintained pro-inflammatory response associated to the delay or the inhibition of tumour growth. PFM administration to mice bearing tumour maintained an important inflammatory response; however, in contrast to the milk group, this response was regulated to avoid exacerbation of inflammation. In the metastasis model, the benefits of PFM were associated to avoid the immunosuppression associated to high interleukin-10 levels. In conclusion, as cancer cells induce modifications of the immune response to favour their own growth at each stage of cancer development, PFM administration stimulated different profile of cytokines to respond to these modifications and fight against cancer cells.

ANDROID APPLICATION FOR DETECTION OF SKIN CANCER USING EXPERT SYSTEM

2018 ◽  
Vol 2 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Yogi Udjaja
Keyword(s):  
Risk Factor ◽  
Expert System ◽  
Skin Cancer ◽  
Cancer Cells ◽  
System Application ◽  
Ultraviolet Rays ◽  
The Sun ◽  
Android Application ◽  
Abnormal Growth ◽  
Skin Cells

Skin cancer is an abnormal growth of human skin that can damage skin cells. By knowing the symptoms of skin cancer as early as posssible, it is helpful in preventing the spread of cancer cells and treatment. There are many factors that cause skin cancer, but in general the cause is exposure to ultraviolet rays from the sun.  Therefore, an expert system application is required to detect skin cancer.  By using backward chining and probalility methode; which data is in form of someone’s risk factor and clinical sympthoms, then the application will provide temporary diagnosis.  This application is built in an android platfrom because in its development android is more used than other platforms. The accuracy obtained from this application is 96.67%.

Identification of BAP1-associated MicroRNAs and Implications in Cancer Development

2019 ◽  
pp. 1-4
Author(s):  
Tikam Chand ◽  
Tikam Chand
Keyword(s):  
Gene Regulation ◽  
In Silico ◽  
Mirna Target ◽  
Target Prediction ◽  
Differential Regulation ◽  
Cancer Development ◽  
Mirna Target Prediction ◽  
Cancer Types ◽  
In Silico Tools

Having role in gene regulation and silencing, miRNAs have been implicated in development and progression of a number of diseases, including cancer. Herein, I present potential miRNAs associated with BAP1 gene identified using in-silico tools such as TargetScan and Exiqon miRNA Target Prediction. I identified fifteen highly conserved miRNA (hsa-miR-423-5p, hsa-miR-3184-5p, hsa-miR-4319, hsa-miR125b-5p, hsa-miR-125a-5p, hsa-miR-6893-3p, hsa-miR-200b-3p, hsa-miR-200c-3p, hsa-miR-505-3p.1, hsa-miR-429, hsa-miR-370-3p, hsa-miR-125a-5p, hsa-miR-141-3p, hsa-miR-200a-3p, and hsa-miR-429) associated with BAP1 gene. We also predicted the differential regulation of these twelve miRNAs in different cancer types.

Sign in / Sign up

Export Citation Format

Share Document