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Human-Specific Elimination of Epithelial Siglec-XII Suppresses the Risk of CRC Initiation and Progression [ENDPOINT]

ABSTRACT: Human-Specific Elimination of Epithelial Siglec-XII Suppresses the Risk of CRC Initiation and Progression [ENDPOINT]

PROVIDER: PRJNA1090216 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28401424_1.fastq.gz	Fastqsanger.gz
	SRR28401424_2.fastq.gz	Fastqsanger.gz
	SRR28401425_1.fastq.gz	Fastqsanger.gz
	SRR28401425_2.fastq.gz	Fastqsanger.gz
	SRR28401426_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Human-Specific Elimination of Epithelial Siglec-XII Suppresses the Risk of CRC Initiation and Progression [ENDPOINT]

Project description:Human-specific changes in specific Siglecs is one of the reasons put forth as molecular mechanisms that could explain human proneness to developing cancers. The SIGLEC12 gene, which encodes the Siglec-XII protein mainly found on epithelial cells, has a fixed homozygous missense mutation in a critical arginine renders unable to recognize its natural ligand. Additionally, the gene harbors a polymorphic frameshift mutation that eliminates expression of the full-length protein in most humans. We hypothesized that dysfunctional Siglec-XII is involved in cancer progression in humans' epithelia. Here we report that the transgenic conditional expression of human Siglec-XII in mouse intestinal epithelia increased the number and size of cancers in a model of colitis-associated colorectal carcinoma (AOM/DSS). RNA sequencing of the colons at baseline and after AOM/DSS challenge derived a gene signature comprised of the differentially expressed genes (DEGs) between controls (Villin1-Cre-ER(T2)) and Siglec-XII-expressing mice, showing that upregulated DEGs in Siglec-XII mice were enriched for diverse bioenergetic processes.

2024-03-27 | GSE262087 | GEO

Human-Specific Elimination of Epithelial Siglec-XII Suppresses the Risk of CRC Initiation and Progression [CACO]

Project description:Human-specific changes in specific Siglecs is one of the reasons put forth as molecular mechanisms that could explain human proneness to developing cancers. The SIGLEC12 gene, which encodes the Siglec-XII protein mainly found on epithelial cells, has a fixed homozygous missense mutation in a critical arginine renders unable to recognize its natural ligand. Additionally, the gene harbors a polymorphic frameshift mutation that eliminates expression of the full-length protein in most humans. We hypothesized that dysfunctional Siglec-XII is involved in cancer progression in humans' epithelia. Here we report that the forced expression of human Siglec-XII in caco-2 cells showed that differentially expressed genes in Siglec-XII cells were enriched for diverse bioenergetic processes.

2024-03-27 | GSE262085 | GEO

Human-Specific Elimination of Epithelial Siglec-XII Suppresses the Risk of CRC Initiation and Progression [baseline]

Project description:Human-specific changes in specific Siglecs is one of the reasons put forth as molecular mechanisms that could explain human proneness to developing cancers. The SIGLEC12 gene, which encodes the Siglec-XII protein mainly found on epithelial cells, has a fixed homozygous missense mutation in a critical arginine renders unable to recognize its natural ligand. Additionally, the gene harbors a polymorphic frameshift mutation that eliminates expression of the full-length protein in most humans. We hypothesized that dysfunctional Siglec-XII is involved in cancer progression in humans' epithelia. Here we report that the transgenic conditional expression of human Siglec-XII in mouse intestinal epithelia did not by itself cause carcinomas and RNA sequencing of the colons at baseline derived a gene signature without differentially expressed genes (DEGs) between controls (Villin1-Cre-ER(T2)) and Siglec-XII-expressing mice

2024-03-27 | GSE262086 | GEO

Human-Specific Elimination of Epithelial Siglec-XII Suppresses the Risk of CRC Initiation and Progression

Project description:Human-Specific Elimination of Epithelial Siglec-XII Suppresses the Risk of CRC Initiation and Progression

| PRJNA1090166 | ENA

Human-Specific Elimination of Epithelial Siglec-XII Suppresses the Risk of CRC Initiation and Progression [baseline]

Project description:Human-Specific Elimination of Epithelial Siglec-XII Suppresses the Risk of CRC Initiation and Progression [baseline]

| PRJNA1090163 | ENA

Human-Specific Elimination of Epithelial Siglec-XII Suppresses the Risk of CRC Initiation and Progression [CACO]

Project description:Human-Specific Elimination of Epithelial Siglec-XII Suppresses the Risk of CRC Initiation and Progression [CACO]

| PRJNA1090164 | ENA

Human-Specific Elimination of Epithelial Siglec-XII Suppresses the Risk of CRC Initiation and Progression

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-03-27 | GSE262088 | GEO

Ablation of collagen XII disturbs joint extracellular matrix organization and causes patellar subluxation

Project description:Collagen XII, belonging to the fibril-associated collagens, is a homotrimeric secreted extracellular matrix (ECM) protein encoded by the COL12A1 gene. Mutations in the human COL12A1 gene cause an Ehlers-Danlos/myopathy overlap syndrome leading to skeletal abnormalities and muscle weakness. Here, we studied the role of collagen XII in joint pathophysiology by analyzing collagen XII deficient mice and human patients. We found that collagen XII is widely expressed across multiple connective tissue of the developing joint. Lack of collagen XII in mice destabilizes tendons and the femoral trochlear groove to induce patellar subluxation in the patellofemoral joint. These changes are associated with an ECM damage response in tendon and secondary quadriceps muscle degeneration. Moreover, patellar subluxation was also identified as a clinical feature of human patients with collagen XII deficiency. The results provide an explanation for joint hyperlaxity in mice and human patients with collagen XII deficiency.

2023-06-19 | GSE234964 | GEO

Siglec-G suppresses CD8+ T cells responses through metabolic rewiring and can be targeted to enhance tumor immunotherapy

Project description:CD8+ T cells play a critical role in cancer immune-surveillance and pathogens elimination. However, their effector function can be severely impaired due to inhibitory receptors such as PD-1 and Tim-3. Here we identify Siglec-G as a novel coinhibitory receptor that limits CD8+ T cell function. Siglec-G is highly expressed on tumor-inﬁltrating T cells and is enriched in the exhausted T cell subset. Ablation of Siglec-G enhances the efficacy of adoptively transferred T cells and CAR T cells to repress the growth of solid tumors. Mechanistically, sialic acids on tumor cells trigger Siglec-G-SHP2 axis in CD8+ T cells, and impairs metabolic reprogramming from OXPHOS to glycolysis, which dampens CTL activation, expansion and cytotoxicity. These findings deﬁne a critical role for Siglec-G in inhibiting CD8+ T cell responses, which strongly suggests its therapeutic effect in adoptive T cell therapy and tumor immunotherapy.

2024-12-18 | GSE272544 | GEO

Human-specific elimination of epithelial Siglec-XII suppresses the risk of inflammation-driven colorectal cancers.

Project description:Carcinomas are common in humans but rare among closely related "great apes." Plausible explanations, including human-specific genomic alterations affecting the biology of sialic acids, are proposed, but causality remains unproven. Here, an integrated evolutionary genetics-phenome-transcriptome approach studied the role of SIGLEC12 gene (encoding Siglec-XII) in epithelial transformation and cancer. Exogenous expression of the protein in cell lines and genetically engineered mice recapitulated approximately 30% of the human population in whom the protein is expressed in a form that cannot bind ligand because of a fixed, homozygous, human-universal missense mutation. Siglec-XII-null cells/mice recapitulated the remaining approximately 70% of the human population in whom an additional polymorphic frameshift mutation eliminates the entire protein. Siglec-XII expression drove several pro-oncogenic phenotypes in cell lines and increased tumor burden in mice challenged with chemical carcinogen and inflammation. Transcriptomic studies yielded a 29-gene signature of Siglec-XII-positive disease and when used as a computational tool for navigating human data sets, pinpointed with surprising precision that SIGLEC12 expression (model) recapitulates a very specific type of colorectal carcinomas (disease) that is associated with mismatch-repair defects and inflammation, disproportionately affects European Americans, and carries a favorable prognosis. They revealed a hitherto-unknown evolutionary genetic mechanism for an ethnic/environmental predisposition of carcinogenesis.

| S-EPMC11343606 | biostudies-literature

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