Molecular and Clinical Relevance of ZBTB38 Expression Levels in Prostate Cancer

Dieuleveult, Maud de; Marchal, Claire; Jouinot, Anne; Letessier, A; Miotto, Benoît

doi:10.3390/cancers12051106

Cited by 8 publications

(9 citation statements)

References 69 publications

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“…We did not observe particular enrichment in GO pathways for APH UP genes (FDR > 0.01). Nevertheless, we noticed an up-regulation of the transcription factor gene ZBTB38 which is a biomarker for prostate cancer (59) and that plays an important role in the regulation of DNA replication, cell cycle and cell fate (60,61). Importantly, the expression of genes that fell inside aRTIL was not affected by low replication stress (Figure 4b).…”

Section: Low Replication Stress Impacts the Regulation Of Genes Involmentioning

confidence: 93%

Low replication stress leads to specific replication timing advances associated to chromatin remodelling in cancer cells

Courtot

Bournique

Maric

et al. 2020

Preprint

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DNA replication is very well orchestrated in mammalian cells due to a tight regulation of the temporal order of replication origin activation, known as the replication timing program. The replication timing of a given replication domain is very robust and well conserved in each cell type. Upon low replication stress, the slowing of replication forks induces delayed replication of some fragile regions leading to DNA damage and genetic instability. Except for these fragile regions, the direct impact of low replication stress on the replication timing in different cellular backgrounds has not been explored in detail. Here we analysed DNA replication timing across the whole genome in a panel of human cell lines in the presence of low replication stress. We demonstrate that low replication stress induced by aphidicolin has a stronger impact on the replication timing of cancer cells than non-tumour cells. Strikingly, we unveiled an enrichment of specific replication domains undergoing a switch from late to early replication in some cancer cells. We found that advances in replication timing correlate with heterochromatin regions poorly sensitive to DNA damage signalling while being subject to an increase of chromatin accessibility in response to aphidicolin. Finally, our data indicate that, following release from replication stress conditions, replication timing advances can be inherited by the next cellular generation, suggesting a new mechanism by which some cancer cells would adapt to cellular or environmental stress.

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Section: Low Replication Stress Impacts the Regulation Of Genes Involmentioning

confidence: 93%

Low replication stress leads to specific replication timing advances associated to chromatin remodelling in cancer cells

Courtot

Bournique

Maric

et al. 2020

Preprint

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“…However, The biological function of ZBTB38 remains also elusive [ 38 ]. In bladder cancer, ZBTB38 promotes migration and invasive growth [ 39 ], while in prostate cancer, depletion of ZBTB38 results in higher expression of ROS and elevated cell death after doxorubicin treatment [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Cisplatin resistance-related multi-omics differences and the establishment of machine learning models

Sui

Chen

et al. 2022

J Transl Med

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Objectives Platinum-based chemotherapies are currently the first-line treatment of non-small cell lung cancer. This study will improve our understanding of the causes of resistance to cisplatin, especially in lung adenocarcinoma (LUAD) and provide a reference for therapeutic decisions in clinical practice. Methods Cancer Cell Line Encyclopedia (CCLE), The Cancer Genome Atlas (TCGA) and Zhongshan hospital affiliated to Fudan University (zs-cohort) were used to identify the multi-omics differences related to platinum chemotherapy. Cisplatin-resistant mRNA and miRNA models were constructed by Logistic regression, classification and regression tree and C4.5 decision tree classification algorithm with previous feature selection performed via least absolute shrinkage and selection operator (LASSO). qRT-PCR and western-blotting of A549 and H358 cells, as well as single-cell Seq data of tumor samples were applied to verify the tendency of certain genes. Results 661 cell lines were divided into three groups according to the IC50 value of cisplatin, and the top 1/3 (220) with a small IC50 value were defined as the sensitive group while the last 1/3 (220) were enrolled in the insensitive group. TP53 was the most common mutation in the insensitive group, in contrast to TTN in the sensitive group. 1348 mRNA, 80 miRNA, and 15 metabolites were differentially expressed between 2 groups (P < 0.05). According to the LASSO penalized logistic modeling, 6 of the 1348 mRNAs, FOXA2, BATF3, SIX1, HOXA1, ZBTB38, IRF5, were selected as the associated features with cisplatin resistance and for the contribution of predictive mRNA model (all of adjusted P-values < 0.001). Three of 6 (BATF3, IRF5, ZBTB38) genes were finally verified in cell level and patients in zs-cohort. Conclusions Somatic mutations, mRNA expressions, miRNA expressions, metabolites and methylation were related to the resistance of cisplatin. The models we created could help in the prediction of the reaction and prognosis of patients given platinum-based chemotherapies.

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“…Other in vivo data on the effects of ZBTB38 on growth are inconsistent with decreased expression seen in mouse models of muscle regeneration [ 18 ] but decreased proliferation seen with Cibz knockdown in mouse embryonic stem cells [ 19 ]. In prostate cancer ZBTB38 expression is lower in tumors compared with benign prostatic hypertrophic and normal tissue, and lower expression is associated with higher pathological grade and poorer outcome [ 24 ]. Depletion of ZBTB38 in prostate cancer cell lines, however, did not alter cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Role of ZBTB38 Genotype and Expression in Growth and Response to Recombinant Human Growth Hormone Treatment

Parsons

Stevens

Whatmore

et al. 2022

Journal of the Endocrine Society

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Background SNPs in ZBTB38 have been associated with idiopathic short stature (ISS) and adult height. This study sought to a) characterise the phenotype of ISS patients and their response to recombinant human growth hormone (rhGH) by ZBTB38 SNP genotype b) describe the relationship of ZBTB38 expression with normal growth and c) describe the in vitro effects of ZBTB38 knockdown on cell proliferation and MCM10 expression. Methods The genotype-phenotype relationship of rs6764769 and rs72401 were explored in 261 ISS patients and effects of genotype on response to rhGH were assessed in 93 patients treated with rhGH. The relationship between age and ZBTB38 expression was assessed in 87 normal children and young adults. Knockdown of ZBTB38 in SiHA cells was achieved with siRNAs and cell proliferation assessed with a WST-8 assay. Results rs6764769 and rs72401 are in linkage disequilibrium. rs724016 GG genotype was associated with lower birth length (p=0.01) and a lower change in height SDS over the first year of treatment (p=0.02). ZBTB38 expression was positively correlated with age (p<0.001). siRNA mediated knockdown of ZBTB38 resulted in increased cell proliferation at 72 and 96 hours post-transfection but did not alter expression of MCM10. Conclusions SNPs within ZBTB38 associated with ISS are linked to higher birth size within a cohort of ISS patients and a better response to rhGH therapy while ZBTB38 expression is positively related to age.

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Molecular and Clinical Relevance of ZBTB38 Expression Levels in Prostate Cancer

Cited by 8 publications

References 69 publications

Low replication stress leads to specific replication timing advances associated to chromatin remodelling in cancer cells

Low replication stress leads to specific replication timing advances associated to chromatin remodelling in cancer cells

Cisplatin resistance-related multi-omics differences and the establishment of machine learning models

Role of ZBTB38 Genotype and Expression in Growth and Response to Recombinant Human Growth Hormone Treatment

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