HspBP1 is a dual function regulatory protein that controls both DNA repair and apoptosis in breast cancer cells

Youn, Cha Kyung; Lee, Jung‐Hee; Hariharasudhan, Gurusamy; Kim, Hong-Beum; Kim, Jeeho; Lee, Sumi; Lim, Sung‐Chul; Yoon, Sang‐Pil; Park, Sang-Gon; Chang, In Youb; You, Ho Jin

doi:10.1038/s41419-022-04766-0

Cited by 9 publications

(6 citation statements)

References 46 publications

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“…Similarly, KDM1A inhibition is effective in reducing stemness and treating TNBC ( 42 ). Decreased HSPBP1 may lead to genomic instability and enables resistance to ionizing radiation in high-grade and metastatic BC ( 43 ). Therefore, these hub genes may associate with ZSCAN18 and play important roles in BC.…”

Section: Discussionmentioning

confidence: 99%

Zinc finger and SCAN domain-containing protein 18 is a potential DNA methylation-modified tumor suppressor and biomarker in breast cancer

Wang

Luo

et al. 2023

Front. Endocrinol.

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IntroductionZinc finger and SCAN domain-containing protein 18 (ZSCAN18) has been investigated as a putative biomarker of multiple human cancers. However, the expression profile, epigenetic modification, prognostic value, transcription regulation, and molecular mechanism of ZSCAN18 in breast cancer (BC) remain unknown.MethodsIn the study, we present an integrated analysis of ZSCAN18 in BC based on public omics datasets with the use of multiple bioinformatics tools. Genes potentially regulated through restoration of ZSCAN18 expression in MDA-MB-231 cells were investigated to identify pathways associated with BC.ResultsWe observed that ZSCAN18 was downregulated in BC and mRNA expression was significantly correlated with clinicopathological parameters. Low expression of ZSCAN18 was found in the HER2-positive and TNBC subtypes. High expression of ZSCAN18 was associated with good prognosis. As compared to normal tissues, the extent of ZSCAN18 DNA methylation was greater with fewer genetic alterations in BC tissues. ZSCAN18 was identified as a transcription factor that might be involved in intracellular molecular and metabolic processes. Low ZSCAN18 expression was associated with the cell cycle and glycolysis signaling pathway. Overexpression of ZSCAN18 inhibited mRNA expression of genes associated with the Wnt/β-catenin and glycolysis signaling pathways, including CTNNB1, BCL9, TSC1, and PFKP. ZSCAN18 expression was negatively correlated with infiltrating B cells and dendritic cells (DCs), as determined by the TIMER web server and reference to the TISIDB. ZSCAN18 DNA methylation was positively correlated with activated B cells, activated CD8+ and CD4+ T cells, macrophages, neutrophils, and activated DCs. Moreover, five ZSCAN18-related hub genes (KDM6B, KAT6A, KMT2D, KDM1A, and HSPBP1) were identified. ZSCAN18, ZNF396, and PGBD1 were identified as components of a physical complex.ConclusionZSCAN18 is a potential tumor suppressor in BC, as expression is modified by DNA methylation and associated with patient survival. In addition, ZSCAN18 plays important roles in transcription regulation, the glycolysis signaling pathway, and the tumor immune microenvironment.

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Section: Discussionmentioning

confidence: 99%

Zinc finger and SCAN domain-containing protein 18 is a potential DNA methylation-modified tumor suppressor and biomarker in breast cancer

Wang

Luo

et al. 2023

Front. Endocrinol.

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“…HspBP1 regulates the phosphorylation of the tumor suppressor BRCA1 and its subsequent recruitment to DNA damage sites. It was recently shown that HspBP1 inhibits, in a BRCA1-dependent manner, the tumorigenesis of breast cancer in vitro and in vivo and promotes apoptosis [ 50 ]. Although we did not observe any clear change in HspBP1 levels between GBM and normal brain tissues, our LC-MS/MS analysis demonstrated ST1926 up-regulated HspBP1 levels in U251 cells.…”

Section: Discussionmentioning

confidence: 99%

The Antitumor Effect of the DNA Polymerase Alpha Inhibitor ST1926 in Glioblastoma: A Proteomics Approach

El-Baba,

Ayache,

Goli

et al. 2023

IJMS

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Glioblastoma Multiforme (GBM) is the most aggressive form of malignant brain tumor. The median survival rate does not exceed two years, indicating an imminent need to develop novel therapies. The atypical adamantyl retinoid ST1926 induces apoptosis and growth inhibition in different cancer types. We have shown that ST1926 is an inhibitor of the catalytic subunit of DNA polymerase alpha (POLA1), which is involved in initiating DNA synthesis in eukaryotic cells. POLA1 levels are elevated in GBM versus normal brain tissues. Therefore, we studied the antitumor effects of ST1926 in several human GBM cell lines. We further explored the global protein expression profiles in GBM cell lines using liquid chromatography coupled with tandem mass spectrometry to identify new targets of ST1926. Low sub-micromolar concentrations of ST1926 potently decreased cell viability, induced cell damage and apoptosis, and reduced POLA1 protein levels in GBM cells. The proteomics profiles revealed 197 proteins significantly differentially altered upon ST1926 treatment of GBM cells involved in various cellular processes. We explored the differential gene and protein expression of significantly altered proteins in GBM compared to normal brain tissues.

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“…Furthermore, there is a recent report on the ratio of iHSP70 to eHSP70 and inflammation [56]. When cells undergo stress, iHSP70 present in cells is transferred to the circulation system through mechanisms such as cell necrosis and ATP-binding cassette (ABC) transporters [57,58]. This HSP was named eHSP70.…”

Section: Chronic Inflammationmentioning

confidence: 99%

Prevention by Heat Stimulation of Metabolic Syndrome Progression Based upon the Underlying Molecular Mechanism

Nagai,

Kaji

2024

Metabolic Syndrome - Lifestyle and Biological Risk Factors

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Metabolic syndrome (MS) is a pathological condition that causes high blood pressure, abnormal glucose metabolism, and lipid metabolism based on visceral fat accumulation. Insulin resistance and atherosclerosis caused by chronic inflammation of visceral adipose tissue are fundamental pathologies of lifestyle-related diseases. It is well known that diet and exercise are important in preventing these diseases. However, exercise is limited in people with various locomotive disorders. In recent years, the use of heat therapy to treat insulin resistance has attracted attention. Many researchers are interested in strengthening the skeletal muscle functions as a metabolic organ. We are verifying the thermal effect of skeletal muscles on underlying mechanism of MS progression such as chronic inflammation, cell death and heat shock protein 70 family (HSP70). This chapter reviews recent reports on whether hyperthermia may safely contribute to the prevention of MS and its progression to type 2 diabetes and atherosclerosis. It was thought that the chaperone function of HSP70 could be used to influence inflammatory cytokines and contribute to the prevention of insulin resistance and atherosclerosis. Thermal effects may be useful, especially when physical activity is limited. Safe and effective interventions to prevent MS and its progression require further research.

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HspBP1 is a dual function regulatory protein that controls both DNA repair and apoptosis in breast cancer cells

Cited by 9 publications

References 46 publications

Zinc finger and SCAN domain-containing protein 18 is a potential DNA methylation-modified tumor suppressor and biomarker in breast cancer

Zinc finger and SCAN domain-containing protein 18 is a potential DNA methylation-modified tumor suppressor and biomarker in breast cancer

The Antitumor Effect of the DNA Polymerase Alpha Inhibitor ST1926 in Glioblastoma: A Proteomics Approach

Prevention by Heat Stimulation of Metabolic Syndrome Progression Based upon the Underlying Molecular Mechanism

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