Downregulation of ANP32B exerts anti-apoptotic effects in hepatocellular carcinoma

Ohno, Yoshinori; Koizumi, Masaru; Nakayama, Haruhiko; Watanabe, Takao; Hirooka, Masashi; Terada, Yoshio; Kuroda, Taira; Abe, Masanori; Fukuda, Shinji; Higashiyama, Shigeki; Kumagi, Teru; Hiasa, Yoichi

doi:10.1371/journal.pone.0177343

Cited by 17 publications

(11 citation statements)

References 39 publications

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“…For example, the transcription factor Krüppel‐like factor 5 can recruit ANP32B to the promoter region of the platelet‐derived growth factor subunit A gene to suppress its expression by incorporating histones and inhibiting its acetylation . On the other hand, it has also been suggested that ANP32B may exert an antiapoptotic function due to the observed correlation between its downregulation in hepatocellular carcinoma cells and the progression of the disease, characterized by the enhanced phosphorylation/activation of Bcl‐2‐associated death promoter and the upregulation of Bax . In a similar fashion to SET/TAF‐Iβ and NRP1, C c may be regulating ANP32B function within the nucleus.…”

Section: Nuclear Localization Is What Matters: Converting CC From a Kmentioning

confidence: 99%

New moonlighting functions of mitochondrial cytochrome c in the cytoplasm and nucleus

et al. 2019

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Cytochrome c (Cc) is a protein that functions as an electron carrier in the mitochondrial respiratory chain. However, Cc has moonlighting roles outside mitochondria driving the transition of apoptotic cells from life to death. When living cells are damaged, Cc escapes its natural mitochondrial environment and, once in the cytosol, it binds other proteins to form a complex named the apoptosome—a platform that triggers caspase activation and further leads to controlled cell dismantlement. Early released Cc also binds to inositol 1,4,5‐triphosphate receptors on the ER membrane, which stimulates further massive Cc release from mitochondria. Besides the well‐characterized binding proteins contributing to the proapoptotic functions of Cc, many novel protein targets have been recently described. Among them, histone chaperones were identified as key partners of Cc following DNA breaks, indicating that Cc might modulate chromatin dynamics through competitive binding to histone chaperones. In this article, we review the ample set of recently discovered antiapoptotic proteins—involved in DNA damage, transcription, and energetic metabolism—reported to interact with Cc in the cytoplasm and even the nucleus upon DNA breaks.

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Section: Nuclear Localization Is What Matters: Converting CC From a Kmentioning

confidence: 99%

New moonlighting functions of mitochondrial cytochrome c in the cytoplasm and nucleus

et al. 2019

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“…A study on breast cancer showed that ANP32B is necessary not only for the normal development of the body but also for the growth of breast cancer cells [ 31 ]. In the only study on ANP32B and HCC, downregulation of ANP32B played an antiapoptotic effect, but upregulation of ANP32B did not lead to apoptosis of HCC cells [ 9 ]. ANP32E can promote cell proliferation in mammals and plays a role in DNA repair and the cell cycle [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we decided to adhere to the view of Reilly et al that only ANP32A, ANP32B, and ANP32E can truly be considered members of the ANP32 family in mammals [7]. Members of the ANP32 family participate in various molecular biological processes, such as embryonic development, chromatin modification and reconstruction, and apoptosis, by regulating cell signals and gene expression [7][8][9]. Many studies have shown that members of the ANP32 family are differentially expressed in certain cancers, such as pancreatic cancer, prostate cancer, breast cancer, glioblastoma, and leukemia, playing tumor-suppressive and oncogenic roles [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

ANP32 Family as Diagnostic, Prognostic, and Therapeutic Biomarker Related to Immune Infiltrates in Hepatocellular Carcinoma

Liu

Wang

et al. 2022

Disease Markers

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Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, with high incidence and mortality rate. There is an urgent need to identify effective diagnostic and prognostic biomarkers for HCC. Members of the acidic leucine-rich nucleophosphoprotein 32 (ANP32) family, which mainly includes ANP32A, ANP32B, and ANP32E, are abnormally expressed and have prognostic value in certain cancers. However, the diagnostic, prognostic, and therapeutic value of ANP32 family members in HCC has not yet been fully studied. In this study, we identified the diagnostic and prognostic value of ANP32 family members in HCC. Transcriptome data from public databases, such as the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, suggested that ANP32A, ANP32B, and ANP32E were upregulated in HCC tissues, and high expression of ANP32 family members was associated with advanced pathologic stage and histologic grade. Our immunohistochemistry and western blot results further verified the differential expression of ANP32 family members. ANP32A, ANP32B, and ANP32E had an outstanding diagnostic potential. Survival analysis of HCC patients in TCGA databases demonstrated that ANP32A, ANP32B, and ANP32E were associated with poor overall survival (OS) and disease-specific survival (DSS). Univariate and multivariate Cox analyses suggested the capability of ANP32B and ANP32E to independently predict the OS and DSS of HCC patients. Gene set enrichment analysis (GSEA) showed that ANP32 family members were associated with immune response, epidermal cell differentiation, and stem cell proliferation. Expression of ANP32 family members was associated with immune cell infiltration and immune status in the tumor microenvironment of HCC, and patients with high ANP32 family expression had poor sensitivity to immunotherapy. Finally, we identified potential chemotherapy drugs for HCC patients with high ANP32 family expression by CellMiner database. This study suggested the diagnostic, prognostic, and therapeutic roles of the ANP32 family in HCC patients, providing potential therapeutic targets for HCC.

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“…The acidic (leucine-rich) nuclear phosphoprotein 32 family member B ( ANP32B ), belong to the acidic nuclear phosphoprotein 32 (ANP32) family. ANP32B can modulate phosphorylation of Bad and expression of Bak/Bax , thus regulating apoptosis in HCC ( 24 ). Repair of damaged DNA relies on nucleosome dismantling of the nucleosome by histone chaperones and de-phosphorylation events carried out by Protein Phospatase 2A (PP2A) ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic and Immune-Cell Infiltration Changes in the Tumor Microenvironment in Hepatocellular Carcinoma

Yang

Wang

et al. 2021

Front. Immunol.

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BackgroundEpigenetics regulate gene expression without altering the DNA sequence. Epigenetics targeted chemotherapeutic approach can be used to overcome treatment resistance and low response rate in HCC. However, a comprehensive review of genomic data was carried out to determine the role of epigenesis in the tumor microenvironment (TME), immune cell-infiltration characteristics in HCC is still insufficient.MethodsThe association between epigenetic-related genes (ERGs), inflammatory response-related genes (IRRGs) and CRISPR genes was determined by merging genomic and CRISPR data. Further, characteristics of immune-cell infiltration in the tumor microenvironment was evaluated.ResultsNine differentially expressed genes (ANP32B, ASF1A, BCORL1, BMI1, BUB1, CBX2, CBX3, CDK1, and CDK5) were shown to be independent prognostic factors based on lasso regression in the TCGA-LIHC and ICGC databases. In addition, the results showed significant differences in expression of PDCD-1 (PD-1) and CTLA4 between the high- and low-epigenetic score groups. The CTRP and PRISM-derived drug response data yielded four CTRP-derived compounds (SB-743921, GSK461364, gemcitabine, and paclitaxel) and two PRISM-derived compounds (dolastatin-10 and LY2606368). Patients with high ERGs benefited more from immune checkpoint inhibitor (ICI) therapy than patients with low ERGs. In addition, the high ERGs subgroup had a higher T cell exclusion score, while the low ERGs subgroup had a higher T cell dysfunction. However, there was no difference in microsatellite instability (MSI) score among the two subgroups. Further, genome-wide CRISPR-based loss-of function screening derived from DepMap was conducted to determine key genes leading to HCC development and progression. In total, 640 genes were identified to be essential for survival in HCC cell lines. The protein-protein interaction (PPI) network demonstrated that IRRGs PSEN1 was linked to most ERGs and CRISPR genes such as CDK1, TOP2A, CBX2 and CBX3.ConclusionEpigenetic alterations of cancer-related genes in the tumor microenvironment play a major role in carcinogenesis. This study showed that epigenetic-related novel biomarkers could be useful in predicting prognosis, clinical diagnosis, and management in HCC.

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Downregulation of ANP32B exerts anti-apoptotic effects in hepatocellular carcinoma

Cited by 17 publications

References 39 publications

New moonlighting functions of mitochondrial cytochrome c in the cytoplasm and nucleus

New moonlighting functions of mitochondrial cytochrome c in the cytoplasm and nucleus

ANP32 Family as Diagnostic, Prognostic, and Therapeutic Biomarker Related to Immune Infiltrates in Hepatocellular Carcinoma

Epigenetic and Immune-Cell Infiltration Changes in the Tumor Microenvironment in Hepatocellular Carcinoma

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