A genome-wide enrichment screen identifies NUMA1-loss as a resistance mechanism against mitotic cell-death induced by BMI1 inhibition

Gisler, Santiago; Maia, Alexandra S.; Chandrasekaran, G.; Kopparam, Jawahar; Lohuizen, Maarten van

doi:10.1371/journal.pone.0227592

Cited by 3 publications

(3 citation statements)

References 54 publications

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“…( Chu et al, 2016 ; Torii et al, 2020 ). The absence of NUMA1 resists cell death in the PTC-318 cell ( Gisler et al, 2020 ), and the alternative splicing of the gene is associated with the cellular proliferation and centrosome amplification in the epithelial cells ( Sebestyén et al, 2016 ). SAFB1 regulates RNA processing and neuronal function rendering the chromatin permissive for DNA damage signaling and myogenic differentiation ( Hernandez-Hernandez et al, 2013 ; Rivers et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Gene Expression Profiles Reveal Distinct Molecular Characteristics of the Goose Granulosa Cells

Gao

Zhang

et al. 2021

Front. Genet.

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Granulosa cells (GCs) are decisive players in follicular development. In this study, the follicle tissues and GCs were isolated from the goose during the peak-laying period to perform hematoxylin-eosin staining and RNA-seq, respectively. Moreover, the dynamic mRNA and lncRNA expression profiles and mRNA-lncRNA network analysis were integrated to identify the important genes and lncRNAs. The morphological analysis showed that the size of the GCs did not significantly change, but the thickness of the granulosa layer cells differed significantly across the developmental stages. Subsequently, 14,286 mRNAs, 3,956 lncRNAs, and 1,329 TUCPs (transcripts with unknown coding potential) were detected in the GCs. We identified 37 common DEGs in the pre-hierarchical and hierarchical follicle stages, respectively, which might be critical for follicle development. Moreover, 3,089 significant time-course DEGs (Differentially expressed genes) and 13 core genes in 4 clusters were screened during goose GCs development. Finally, the network lncRNA G8399 with CADH5 and KLF2, and lncRNA G8399 with LARP6 and EOMES were found to be important for follicular development in GCs. Thus, the results would provide a rich resource for elucidating the reproductive biology of geese and accelerate the improvement of the egg-laying performance of geese.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Gene Expression Profiles Reveal Distinct Molecular Characteristics of the Goose Granulosa Cells

Gao

Zhang

et al. 2021

Front. Genet.

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“…To study the role of kinase deregulation in tumor initiation and/or progression, Robinson-Garcia et al developed a CRISPR-Cas9 systematic approach to identify synthetic lethal interactions for kinase deficiencies to different DNA-damaging chemotherapeutic agents using HAP1 (Robinson-Garcia et al, 2019). Another technique to exploit synthetic lethality in HAP1 was conducted by Gisler et al, by performing a genome-wide screen for gene disruptors that could result in resistance to pharmacological inhibition of BMI1 on HAP1 by exposing mutagenized HAP1 to low concentrations of the BMI1-inhibitor PTC-318 (Gisler et al, 2020).…”

Section: Oncologymentioning

confidence: 99%

HAP1, a new revolutionary cell model for gene editing using CRISPR-Cas9

Llargués-Sistac

Bonjoch

Castellví–Bel

2023

Front. Cell Dev. Biol.

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The use of next-generation sequencing (NGS) technologies has been instrumental in the characterization of the mutational landscape of complex human diseases like cancer. But despite the enormous rise in the identification of disease candidate genetic variants, their functionality is yet to be fully elucidated in order to have a clear implication in patient care. Haploid human cell models have become the tool of choice for functional gene studies, since they only contain one copy of the genome and can therefore show the unmasked phenotype of genetic variants. Over the past few years, the human near-haploid cell line HAP1 has widely been consolidated as one of the favorite cell line models for functional genetic studies. Its rapid turnover coupled with the fact that only one allele needs to be modified in order to express the subsequent desired phenotype has made this human cell line a valuable tool for gene editing by CRISPR-Cas9 technologies. This review examines the recent uses of the HAP1 cell line model in functional genetic studies and high-throughput genetic screens using the CRISPR-Cas9 system. It covers its use in an attempt to develop new and relevant disease models to further elucidate gene function, and create new ways to understand the genetic basis of human diseases. We will cover the advantages and potential of the use of CRISPR-Cas9 technology on HAP1 to easily and efficiently study the functional interpretation of gene function and human single-nucleotide genetic variants of unknown significance identified through NGS technologies, and its implications for changes in clinical practice and patient care.

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“…Several studies have documented that BMI-1 overexpression is inversely correlated to the expression of tumor suppressor genes such as PTEN and p16 [ 30 ]. Gisler et al [ 31 ] have shown that upregulation of BMI-1 significantly induces cancer cells proliferation. Furthermore, it has been shown that elevated BMI-1 mRNA level contributes to anti-cancer drugs resistance.…”

Section: Main Textmentioning

confidence: 99%

Comparative evaluation of BMI-1 proto-oncogene expression in normal tissue, adenoma and papillary carcinoma of human thyroid in pathology samples

2021

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Objective Papillary Thyroid carcinoma accounts for more than 60% of adult thyroid carcinomas. Finding a helpful marker is vital to determine the correct treatment approach. The present study was aimed to evaluate the expression of the B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) gene in papillary carcinoma, adenoma, and adjacent healthy thyroid tissues. Pathology blocks of thyroid tissues at the pathology department of patients who have undergone thyroid surgery between 2015 and 2019 were examined; papillary carcinoma, adenoma, and healthy tissues were selected and sectioned. Total RNA was extracted, and the relative expression level of the BMI-1 gene was examined using the Real-Time qPCR method. Results In the papillary and adenoma tissues, BMI-1 was overexpressed (1.047-fold and 1.042-fold) in comparison to healthy tissues (p < 0.05 for both comparisons). However, no statistically significant differences were observed between adenoma and papillary carcinoma tissues regarding BMI-1 gene expression. This study demonstrated a new biomarker for thyroid malignancies and found that the mRNA levels of the BMI-1 gene were higher in tumor tissues compared with healthy tissues. Further studies are needed to evaluate the BMI1 gene expression in other thyroid cancers.

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A genome-wide enrichment screen identifies NUMA1-loss as a resistance mechanism against mitotic cell-death induced by BMI1 inhibition

Cited by 3 publications

References 54 publications

Genome-Wide Gene Expression Profiles Reveal Distinct Molecular Characteristics of the Goose Granulosa Cells

Genome-Wide Gene Expression Profiles Reveal Distinct Molecular Characteristics of the Goose Granulosa Cells

HAP1, a new revolutionary cell model for gene editing using CRISPR-Cas9

Comparative evaluation of BMI-1 proto-oncogene expression in normal tissue, adenoma and papillary carcinoma of human thyroid in pathology samples

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