Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE262088 | GEO | 2024/03/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

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 [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 [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

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 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

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

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

| PRJNA1090216 | 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

RETRACTED: METTL14 Suppresses CRC Progression via Regulating N6-Methyladenosine-Dependent Primary miR-375 Processing

Project description: Not available

| S-EPMC7001002 | biostudies-literature

BCCIP suppresses tumor initiation but is required for tumor progression.

Project description:Dysfunctions of genome caretaker genes contribute to genomic instability and tumor initiation. Because many of the caretaker genes are also essential for cell viability, permanent loss of function of these genes would prohibit further tumor progression. How essential caretaker genes contribute to tumorigenesis is not fully understood. Here, we report a "hit-and-run" mode of action for an essential caretaker gene in tumorigenesis. Using a BRCA2-interacting protein BCCIP as the platform, we found that a conditional BCCIP knockdown and concomitant p53 deletion caused rapid development of medulloblastomas, which bear a wide spectrum of alterations involving the Sonic Hedgehog (Shh) pathway, consistent with a caretaker responsibility of BCCIP on genomic integrity. Surprisingly, the progressed tumors have spontaneously lost the transgenic BCCIP knockdown cassette and restored BCCIP expression. Thus, a transient downregulation of BCCIP, but not necessarily a permanent mutation, is sufficient to initiate tumorigenesis. After the malignant transformation has been accomplished and autonomous cancer growth has been established, BCCIP reverses its role from a tumor-initiation suppressor to become a requisite for progression. This exemplifies a new type of tumor suppressor, which is distinct from the classical tumor suppressors that are often permanently abrogated during tumorigenesis. It has major implications on how a nonmutagenic or transient regulation of essential caretaker gene contributes to tumorigenesis. We further suggest that BCCIP represents a paradoxical class of modulators for tumorigenesis as a suppressor for initiation but a requisite for progression (SIRP).

| S-EPMC3918420 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data