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Cytosolic DNA composition is determined by genomic instability mechanism and regulates dendritic cell-mediated anti-tumor immunity.

Cell Rep

January 2025

Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2R3, Canada. Electronic address:

Patients with colorectal cancers (CRCs) that have microsatellite instability (MSI) (MSI CRCs) face a better prognosis than those with the more common chromosomal instability (CIN) subtype (CIN CRCs) due to improved T cell-mediated anti-tumor immune responses. Previous investigations identified the cytosolic DNA (cyDNA) sensor STING as necessary for chemokine-mediated T cell recruitment in MSI CRCs. Here, we find that cyDNA from MSI CRC cells is inherently more capable of inducing STING activation and improves cytotoxic T cell activation by dendritic cells (DCs).

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Introduction: We conducted a panoramic analysis of GBN5 expression and prognosis in 33 cancers, aiming to deepen the systematic understanding of GBN5 in cancer.

Materials And Methods: We employed a multi-omics approach, including transcriptomic, genomic, proteomic, single-cell cytomic, spatial transcriptomic, and genomic data, to explore the prognostic value and potential oncogenic mechanisms of GBN5 across pan-cancers from multiple perspectives.

Results: We found that GBN5 was differentially expressed in multiple tumors and showed early diagnostic value.

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HP1 Promotes the Centromeric Localization of ATRX and Protects Cohesion by Interfering Wapl Activity in Mitosis.

Front Biosci (Landmark Ed)

January 2025

The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Hunan Normal University Health Science Center, 410013 Changsha, Hunan, China.

Background: α thalassemia/mental retardation syndrome X-linked (ATRX) serves as a part of the sucrose nonfermenting 2 (SNF2) chromatin-remodeling complex. In interphase, ATRX localizes to pericentromeric heterochromatin, contributing to DNA double-strand break repair, DNA replication, and telomere maintenance. During mitosis, most ATRX proteins are removed from chromosomal arms, leaving a pool near the centromere region in mammalian cells, which is critical for accurate chromosome congression and sister chromatid cohesion protection.

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The Impact of the Metabolic Syndrome Severity on the Appearance of Primary and Permanent DNA Damage.

Medicina (Kaunas)

December 2024

Department of Internal Medicine, Division of Endocrinology, University Hospital Centre Zagreb, Croatian Referral Center for Obesity Treatment, Kišpatićeva 12, 10000 Zagreb, Croatia.

The prevalence of metabolic syndrome (MetS) worldwide is rapid and significant on a global scale. A 2022 meta-analysis of data from 28 million individuals revealed a global prevalence of 45.1%, with notably higher rates in the Eastern Mediterranean Region and the Americas, particularly in high-income countries.

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From Genes to Clinical Practice: Exploring the Genomic Underpinnings of Endometrial Cancer.

Cancers (Basel)

January 2025

SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Research Institute (PACRI), University of Pretoria, Hartfield, Pretoria 0028, South Africa.

Endometrial cancer (EC), a prevalent gynecological malignancy, presents significant challenges due to its genetic complexity and heterogeneity. The genomic landscape of EC is underpinned by genetic alterations, such as mutations in PTEN, PIK3CA, and ARID1A, and chromosomal abnormalities. The identification of molecular subtypes-POLE ultramutated, microsatellite instability (MSI), copy number low, and copy number high-illustrates the diverse genetic profiles within EC and underscores the need for subtype-specific therapeutic strategies.

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