ZNF92, an unexplored transcription factor with remarkably distinct breast cancer over-expression associated with prognosis and cell-of-origin

Kamran, Mohammad; Bhattacharya, Udayan; Omar, Mohamed; Marchionni, Luigi; Ince, Tan A.

doi:10.1038/s41523-022-00474-2

Cited by 3 publications

(1 citation statement)

References 102 publications

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“…Amplification of CACNG4 has been shown to contribute to increased breast cancer cell motility, transformation, and metastasis, highlighting the importance of targeted therapies that can disrupt its actions [ 25 ]. As CACNG4 is located on the plasma membrane, antibody-based therapies have the potential to inhibit its function and impede breast cancer progression, providing a viable and valuable approach for the development of novel treatment strategies.…”

Section: Discussionmentioning

confidence: 99%

Unveiling promising breast cancer biomarkers: an integrative approach combining bioinformatics analysis and experimental verification

Golestan,

Tahmasebi,

Maghsoodi

et al. 2024

BMC Cancer

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Background Breast cancer remains a significant health challenge worldwide, necessitating the identification of reliable biomarkers for early detection, accurate prognosis, and targeted therapy. Materials and methods Breast cancer RNA expression data from the TCGA database were analyzed to identify differentially expressed genes (DEGs). The top 500 up-regulated DEGs were selected for further investigation using random forest analysis to identify important genes. These genes were evaluated based on their potential as diagnostic biomarkers, their overexpression in breast cancer tissues, and their low median expression in normal female tissues. Various validation methods, including online tools and quantitative Real-Time PCR (qRT-PCR), were used to confirm the potential of the identified genes as breast cancer biomarkers. Results The study identified four overexpressed genes (CACNG4, PKMYT1, EPYC, and CHRNA6) among 100 genes with higher importance scores. qRT-PCR analysis confirmed the significant upregulation of these genes in breast cancer patients compared to normal samples. Conclusions These findings suggest that CACNG4, PKMYT1, EPYC, and CHRNA6 may serve as valuable biomarkers for breast cancer diagnosis, and PKMYT1 may also have prognostic significance. Furthermore, CACNG4, CHRNA6, and PKMYT1 show promise as potential therapeutic targets. These findings have the potential to advance diagnostic methods and therapeutic approaches for breast cancer.

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Section: Discussionmentioning

confidence: 99%

Unveiling promising breast cancer biomarkers: an integrative approach combining bioinformatics analysis and experimental verification

Golestan,

Tahmasebi,

Maghsoodi

et al. 2024

BMC Cancer

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Nucleosome reorganisation in breast cancer tissues

Jacob,

Guiblet,

Mamayusupova

et al. 2024

Clin Epigenet

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Background Nucleosome repositioning in cancer is believed to cause many changes in genome organisation and gene expression. Understanding these changes is important to elucidate fundamental aspects of cancer. It is also important for medical diagnostics based on cell-free DNA (cfDNA), which originates from genomic DNA regions protected from digestion by nucleosomes. Results We have generated high-resolution nucleosome maps in paired tumour and normal tissues from the same breast cancer patients using MNase-assisted histone H3 ChIP-seq and compared them with the corresponding cfDNA from blood plasma. This analysis has detected single-nucleosome repositioning at key regulatory regions in a patient-specific manner and common cancer-specific patterns across patients. The nucleosomes gained in tumour versus normal tissue were particularly informative of cancer pathways, with ~ 20-fold enrichment at CpG islands, a large fraction of which marked promoters of genes encoding DNA-binding proteins. The tumour tissues were characterised by a 5–10 bp decrease in the average distance between nucleosomes (nucleosome repeat length, NRL), which is qualitatively similar to the differences between pluripotent and differentiated cells. This effect was correlated with gene activity, differential DNA methylation and changes in local occupancy of linker histone variants H1.4 and H1X. Conclusions Our study offers a novel resource of high-resolution nucleosome maps in breast cancer patients and reports for the first time the effect of systematic decrease of NRL in paired tumour versus normal breast tissues from the same patient. Our findings provide a new mechanistic understanding of nucleosome repositioning in tumour tissues that can be valuable for patient diagnostics, stratification and monitoring.

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Cell-of-Origin Targeted Drug Repurposing for Triple-Negative and Inflammatory Breast Carcinoma with HDAC and HSP90 Inhibitors Combined with Niclosamide

Bhattacharya

Kamran

Manai

et al. 2023

Cancers

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We recently identified a cell-of-origin-specific mRNA signature associated with metastasis and poor outcome in triple-negative carcinoma (TNBC). This TNBC cell-of-origin signature is associated with the over-expression of histone deacetylases and zinc finger protein HDAC1, HDAC7, and ZNF92, respectively. Based on this signature, we discovered that the combination of three drugs (an HDAC inhibitor, an anti-helminthic Niclosamide, and an antibiotic Tanespimycin that inhibits HSP90) synergistically reduces the proliferation of the twelve tested TNBC cell lines. Additionally, we discovered that four out of five inflammatory breast carcinoma cell lines are sensitive to this combination. Significantly, the concentration of the drugs that are used in these experiments are within or below clinically achievable dose, and the synergistic activity only emerged when all three drugs were combined. Our results suggest that HDAC and HSP90 inhibitors combined with the tapeworm drug Niclosamide can achieve remarkably synergistic inhibition of TNBC and IBC. Since Niclosamide, HDAC, and HSP90 inhibitors were approved for clinical use for other cancer types, it may be possible to repurpose their combination for TNBC and IBC.

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ZNF92, an unexplored transcription factor with remarkably distinct breast cancer over-expression associated with prognosis and cell-of-origin

Cited by 3 publications

References 102 publications

Unveiling promising breast cancer biomarkers: an integrative approach combining bioinformatics analysis and experimental verification

Unveiling promising breast cancer biomarkers: an integrative approach combining bioinformatics analysis and experimental verification

Nucleosome reorganisation in breast cancer tissues

Cell-of-Origin Targeted Drug Repurposing for Triple-Negative and Inflammatory Breast Carcinoma with HDAC and HSP90 Inhibitors Combined with Niclosamide

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