Zebrafish in Translational Cancer Research: Insight into Leukemia, Melanoma, Glioma and Endocrine Tumor Biology

Idilli, Aurora; Precazzini, Francesca; Mione, Marina; Anelli, Viviana

doi:10.3390/genes8090236

Cited by 34 publications

(18 citation statements)

References 146 publications

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“…As novel functions of TERRA and different biological processes in which it participates are being proposed and discovered, understanding the specific mechanisms of action of TERRA may become more challenging. Since TERRA expression is highly conserved through evolution [57], the use of model organisms such as mice [141] or zebrafish [142] may become a powerful tool to study TERRA and to understand its function and mechanisms of action. In doing so, it should be considered that the dynamics and functions of TERRA may not be conserved among the different models.…”

Section: Discussionmentioning

confidence: 99%

The Emerging Roles of TERRA in Telomere Maintenance and Genome Stability

Bettin

Pegorar

Cusanelli

2019

Cells

131

107

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The finding that transcription occurs at chromosome ends has opened new fields of study on the roles of telomeric transcripts in chromosome end maintenance and genome stability. Indeed, the ends of chromosomes are required to be protected from activation of DNA damage response and DNA repair pathways. Chromosome end protection is achieved by the activity of specific proteins that associate with chromosome ends, forming telomeres. Telomeres need to be constantly maintained as they are in a heterochromatic state and fold into specific structures (T-loops), which may hamper DNA replication. In addition, in the absence of maintenance mechanisms, chromosome ends shorten at every cell division due to limitations in the DNA replication machinery, which is unable to fully replicate the extremities of chromosomes. Altered telomere structure or critically short chromosome ends generate dysfunctional telomeres, ultimately leading to replicative senescence or chromosome instability. Telomere biology is thus implicated in multiple human diseases, including cancer. Emerging evidence indicates that a class of long noncoding RNAs transcribed at telomeres, known as TERRA for “TElomeric Repeat-containing RNA,” actively participates in the mechanisms regulating telomere maintenance and chromosome end protection. However, the molecular details of TERRA activities remain to be elucidated. In this review, we discuss recent findings on the emerging roles of TERRA in telomere maintenance and genome stability and their implications in human diseases.

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Section: Discussionmentioning

confidence: 99%

The Emerging Roles of TERRA in Telomere Maintenance and Genome Stability

Bettin

Pegorar

Cusanelli

2019

Cells

131

107

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“…Zebrafish is a model species that is widely used in biomedical research, including research about cancer [ 46 , 47 , 48 ]. The existence of two pten genes ( ptena and ptenb ) in zebrafish could make it difficult to use this model to study the effect of Pten mutations in cancer due to the lethality of the double homozygous mutation ( ptena −/− ptenb −/− ) at early developmental stages and the existence of redundant functions between both proteins [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Zebrafish pten Genes Play Relevant but Distinct Roles in Antiviral Immunity

2020

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The PTEN (phosphatase and TENsin homolog on chromosome 10) gene encodes a bifunctional phosphatase that acts as a tumor suppressor. However, PTEN has been implicated in different immune processes, including autophagy, inflammation, regulation of natural killer (NK) cell cytolytic activity and type I interferon responses. Unlike mammals, zebrafish possess two pten genes (ptena and ptenb). This study explores the involvement of both zebrafish pten genes in antiviral defense. Although ptena−/− and ptenb−/− larvae were more susceptible to Spring viremia of carp virus (SVCV), the viral replication rate was lower in the mutant larvae than in the wild-type larvae. We observed that both mutant lines showed alterations in the transcription of numerous genes, including those related to the type I interferon (IFN) system, cytolytic activity, autophagy and inflammation, and some of these genes were regulated in opposite ways depending on which pten gene was mutated. Even though the lower replication rate of SVCV could be associated with impaired autophagy in the mutant lines, the higher mortality observed in the ptena−/− and ptenb−/− larvae does not seem to be associated with an uncontrolled inflammatory response.

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“…The number of models (including mutant and reporter lines) is growing (see Figure 1 for a network of DDR-related zebrafish tools, linked to ZFIN pathway database). This is mostly due to the recent addition of somatic transgenics (reviewed in Idilli et al, 2017; Callahan et al, 2018) and somatic knock outs (Ablain et al, 2015; Di Donato et al, 2016). Reporters of DDR and different DNA repair systems are being perfected, while more tools for detection (antibodies, techniques, etc.)…”

Section: Discussionmentioning

confidence: 99%

The Zebrafish as an Emerging Model to Study DNA Damage in Aging, Cancer and Other Diseases

Cayuela

Claes

Ferreira

et al. 2019

Front. Cell Dev. Biol.

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Cancer is a disease of the elderly, and old age is its largest risk factor. With age, DNA damage accumulates continuously, increasing the chance of malignant transformation. The zebrafish has emerged as an important vertebrate model to study these processes. Key mechanisms such as DNA damage responses and cellular senescence can be studied in zebrafish throughout its life course. In addition, the zebrafish is becoming an important resource to study telomere biology in aging, regeneration and cancer. Here we review some of the tools and resources that zebrafish researchers have developed and discuss their potential use in the study of DNA damage, cancer and aging related diseases.

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Zebrafish in Translational Cancer Research: Insight into Leukemia, Melanoma, Glioma and Endocrine Tumor Biology

Cited by 34 publications

References 146 publications

The Emerging Roles of TERRA in Telomere Maintenance and Genome Stability

The Emerging Roles of TERRA in Telomere Maintenance and Genome Stability

Zebrafish pten Genes Play Relevant but Distinct Roles in Antiviral Immunity

The Zebrafish as an Emerging Model to Study DNA Damage in Aging, Cancer and Other Diseases

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