Dataset Information

Identification of ?-catenin target genes in colorectal cancer by interrogating gene fitness screening data.

ABSTRACT: ?-catenin regulates its target genes which are associated with proliferation, differentiation, migration and angiogenesis, and the dysregulation of Wnt/?-catenin signaling facilitates hallmarks of colorectal cancer (CRC). Identification of ?-catenin targets and their potential roles in tumorigenesis has gained increased interest. However, the number of identified targets remains limited. The present study implemented a novel strategy, interrogating gene fitness profiles derived from large-scale RNA interference and CRISPR-CRISPR associated protein 9 screening data to identify ?-catenin target genes in CRC cell lines. Using these data sets, pair wise gene fitness similarities were determined which highlighted a total of 13 genes whose functions were highly correlated with ?-catenin. It was further demonstrated that the expression of these genes were altered in CRC, illustrating their potential roles in the progression of CRC. The present study further demonstrated that these targets could be used to predict disease-free survival in CRC. In conclusion, the findings provided novel approaches for the identification of ?-catenin targets, which may become prognostic biomarkers or drug targets for the management of CRC.

SUBMITTER: Zhao H

PROVIDER: S-EPMC6733007 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Publications

Identification of β-catenin target genes in colorectal cancer by interrogating gene fitness screening data.

Zhao Haomin H He Liang L Yin Dexin D Song Bin B

Oncology letters 20190806 4

β-catenin regulates its target genes which are associated with proliferation, differentiation, migration and angiogenesis, and the dysregulation of Wnt/β-catenin signaling facilitates hallmarks of colorectal cancer (CRC). Identification of β-catenin targets and their potential roles in tumorigenesis has gained increased interest. However, the number of identified targets remains limited. The present study implemented a novel strategy, interrogating gene fitness profiles derived from large-scale ...[more]

PMID: 31516589

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Project description:Glioblastoma multiforme (GBM) is the most prevalent type of adult brain tumor, and one of the deadliest tumors known to mankind. The genetic understanding of GBM is, however, limited, and the molecular mechanisms which facilitate GBM cell survival and growth within the tumor microenvironment are largely unknown. We applied digital karyotyping and single nucleotide polymorphism (SNP) arrays to screen for copy number changes in GBM samples and found that the most frequently amplified region is at chromosome 7p11.2. The high resolution of digital karyotyping and SNP arrays permits the precise delineation of amplicon boundaries and has enabled identification of the minimal region of amplification at 7p11.2, which contains two genes, EGFR and SEC61?. SEC61? encodes a subunit of a heterotrimeric protein channel located in the endoplasmic reticulum (ER). In addition to its high frequency of gene amplification in GBMs, SEC61? is also remarkably overexpressed in 77% of GBMs, but not in lower-grade gliomas. The siRNA-mediated knockdown of SEC61? expression in tumor cells led to growth suppression and apoptosis. Furthermore, we showed that pharmacological ER stress agents induce SEC61? expression in GBM cells. Together, these results indicate that aberrant expression of SEC61? serves significant roles in GBM cell survival, likely via a mechanism that is involved in the cytoprotective ER stress-adaptive response to the tumor microenvironment. hSETD1A was silenced in HCT116 cells using retrovirus harboring shRNA specifically against the hSETD1A gene. 10?g RNA was reverse transcribed to cDNA using the Applied Biosystems High Capacity cDNA Reverse Transcription kit according to the manufacturer’s instructions (Applied Biosystems). cDNA products were treated with 100ng RNaseA and then purified using the Qiagen PCR purification kit according to the manufacturer’s instructions. NimbleGen Human Gene Expression array was purchased from Roche Applied Sciences. cDNA samples were labeled, Cy3 hybridized, and processed at the FSU NimbleGen Microarray Facility at Florida State University.

Dataset Information

Identification of ?-catenin target genes in colorectal cancer by interrogating gene fitness screening data.

Publications

Identification of β-catenin target genes in colorectal cancer by interrogating gene fitness screening data.

Similar Datasets

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