RBL1 (p107) functions as tumor suppressor in glioblastoma and small-cell pancreatic neuroendocrine carcinoma DOI Open Access
Thomas Naert, Dionysia Dimitrakopoulou, Dieter Tulkens

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2019, Номер unknown

Опубликована: Янв. 23, 2019

Abstract Alterations of the retinoblastoma and/or p53 signaling network are associated with specific cancers such as high-grade astrocytoma/glioblastoma, small cell lung cancer (SCLC), choroid plexus tumors and small-cell pancreatic neuroendocrine carcinoma (SC-PaNEC). However, intricate functional compensation between RB1 related pocket proteins RBL1/p107 RBL2/p130 in suppressing tumorigenesis remains poorly understood. Here we performed lineage-restricted parallel inactivation rb1 rbl1 by multiplex CRISPR/Cas9 genome editing true diploid Xenopus tropicalis to gain insight into these vivo compensatory mechanisms. We show that while is sufficient induce papilloma, combined required drive SC-PaNEC, astrocytoma. Further, using a novel Li-Fraumeni syndrome-mimicking tp53 mutant X. line, demonstrate increased malignancy retinoblastoma-mutant neural malignancies upon concomitant . Interestingly, although clinical SC-PaNEC samples characterized abnormal expression or localization, current experimental models, status had little effect on establishment growth but may rather be essential for maintaining chromosomal stability. SCLC was only rarely observed our set-up, indicating requirement additional alternative oncogenic insults. In conclusion, used delineate tumor suppressor properties Rbl1 generate new insights within protein family cancers.

Язык: Английский

<b><i>Xenopus</i></b>: An Undervalued Model Organism to Study and Model Human Genetic Disease DOI Open Access
Martin Blum, Tim Ott

Cells Tissues Organs, Год журнала: 2018, Номер 205(5-6), С. 303 - 313

Опубликована: Янв. 1, 2018

The function of normal and defective candidate genes for human genetic diseases, which are rapidly being identified in large numbers by geneticists the biomedical community at large, will be best studied relevant predictive model organisms that allow high-speed verification, analysis underlying developmental, cellular molecular mechanisms, establishment disease models to test therapeutic options. We describe discuss pros cons frog Xenopus, has been extensively used uncover developmental mechanisms past, but is underutilized as a model. argue Xenopus complements more commonly mouse zebrafish time- cost-efficient animal study alleles mechanisms.

Язык: Английский

Процитировано

84

CRISPR/Cas9 disease models in zebrafish and Xenopus: The genetic renaissance of fish and frogs DOI
Thomas Naert, Kris Vleminckx

Drug Discovery Today Technologies, Год журнала: 2018, Номер 28, С. 41 - 52

Опубликована: Июль 31, 2018

Язык: Английский

Процитировано

41

Genome-editing approaches and applications: a brief review on CRISPR technology and its role in cancer DOI

Narmadhaa Siva,

Sonal Gupta,

Ayam Gupta

и другие.

3 Biotech, Год журнала: 2021, Номер 11(3)

Опубликована: Фев. 26, 2021

Язык: Английский

Процитировано

9

Potential Roles of the Retinoblastoma Protein in Regulating Genome Editing DOI Creative Commons
Yuning Jiang, Wai Kit Chu

Frontiers in Cell and Developmental Biology, Год журнала: 2018, Номер 6

Опубликована: Июль 31, 2018

Genome editing is an important tool for modifying genomic DNA through introducing insertion or deletion at specific locations of a genome. Recently CRISPR/Cas9 has been widely employed to improve the efficiency genome editing. The Cas9 nuclease creates site-specific double strand breaks (DSBs) targeted loci in Subsequently, DSBs are repaired by two pathways: Homologous Recombination (HR) and Non-Homologous End-Joining (NHEJ). HR considered as "error-free" because it repairs copying sequences from homologous template, while NHEJ "error-prone" there base deletions insertions breakage site. Recently, RB1, gene that commonly mutated retinoblastoma, reported affect repair efficiencies NHEJ. This review focuses on roles RB1 repairing DSBs, which have impacts precision consequences editing, both overall

Язык: Английский

Процитировано

6

RBL1 (p107) functions as tumor suppressor in glioblastoma and small-cell pancreatic neuroendocrine carcinoma DOI Open Access
Thomas Naert, Dionysia Dimitrakopoulou, Dieter Tulkens

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2019, Номер unknown

Опубликована: Янв. 23, 2019

Abstract Alterations of the retinoblastoma and/or p53 signaling network are associated with specific cancers such as high-grade astrocytoma/glioblastoma, small cell lung cancer (SCLC), choroid plexus tumors and small-cell pancreatic neuroendocrine carcinoma (SC-PaNEC). However, intricate functional compensation between RB1 related pocket proteins RBL1/p107 RBL2/p130 in suppressing tumorigenesis remains poorly understood. Here we performed lineage-restricted parallel inactivation rb1 rbl1 by multiplex CRISPR/Cas9 genome editing true diploid Xenopus tropicalis to gain insight into these vivo compensatory mechanisms. We show that while is sufficient induce papilloma, combined required drive SC-PaNEC, astrocytoma. Further, using a novel Li-Fraumeni syndrome-mimicking tp53 mutant X. line, demonstrate increased malignancy retinoblastoma-mutant neural malignancies upon concomitant . Interestingly, although clinical SC-PaNEC samples characterized abnormal expression or localization, current experimental models, status had little effect on establishment growth but may rather be essential for maintaining chromosomal stability. SCLC was only rarely observed our set-up, indicating requirement additional alternative oncogenic insults. In conclusion, used delineate tumor suppressor properties Rbl1 generate new insights within protein family cancers.

Язык: Английский

Процитировано

1