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In silico analysis of DND1 and its co-expressed genes in human cancers
Yun Zhang1, Yafang Li2, Dhruv Chachad3
1Department of Pharmaceutical Sciences, Joan M. Lafleur College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, 77004, USA.
Abstract:
Dead-End (DND1) is an RNA-binding protein involved in translational regulation. Defects in DND1 gene causes germ cell tumors and sterility in rodents. Experimental studies with human somatic cancer cells indicate that DND1 has anti-proliferative and pro-apoptotic function in some while oncogenic function in other cells. We examined The Cancer Genome Atlas data for gene alterations and gene expression changes in DND1 in a variety of human cancers. We found that DND1 is amplified, deleted or mutated in multiple human cancers. In different cancers, DND1 alteration correlates with increased diagnosis age of patients, shift in tumor spectrum or change of tumor sites and in some cases is significantly associated with worse survival for cancer patients. For 15 cancers, we retrieved expression data of thousands of genes that co-expressed with DND1. We found that these cancers contain different percentage of genes that are positively or negatively co-expressed with DND1. Ingenuity Pathway Analysis was performed to explore the biological implications of these genes. More than 10 canonical pathways were identified and each cancer type exhibits unique pathway profiles. Comparison analysis across all 15 cancer types showed that some cancers exhibit strikingly similar profiles of DND1-correlated signaling pathway activation or suppression. Our data reinforce the notion that the biological role of DND1 is cell-type specific and suggest that DND1 may play opposing role by exerting anti-proliferative effects in some cancer cells while being pro-proliferative in others. Our study provides valuable insights to direct experimental investigations of DND1 function in somatic cancers.
Insights
Dead-End (DND1) protein
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Dead-End (DND1) is an RNA-binding protein regulating translation.
- DND1 gene defects are linked to germ cell tumors and sterility in rodents.
- DND1 exhibits context-dependent anti-proliferative or oncogenic functions in human cancer cells.
Purpose of the Study:
- To investigate gene alterations and expression changes of DND1 in human cancers using The Cancer Genome Atlas (TCGA) data.
- To explore the biological implications of DND1 co-expressed genes and pathways across various cancer types.
- To elucidate the cell-type specific role of DND1 in somatic cancers.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) data for DND1 gene alterations (amplification, deletion, mutation) and expression.
- Identification and analysis of genes co-expressed with DND1 across 15 human cancer types.
- Ingenuity Pathway Analysis (IPA) to explore canonical pathways associated with DND1 co-expression profiles.
Main Results:
- DND1 alterations (amplification, deletion, mutation) are prevalent in multiple human cancers.
- DND1 alterations correlate with patient age, tumor spectrum/site shifts, and in some cases, worse survival.
- Co-expression analysis revealed distinct patterns of positively and negatively correlated genes and unique pathway profiles across cancer types, with some cancers showing similar pathway signatures.
Conclusions:
- The biological role of DND1 is cell-type specific, potentially acting as an anti-proliferative factor in some cancers and a pro-proliferative factor in others.
- DND1's complex role in somatic cancers warrants further experimental investigation.
- This study provides insights into DND1's function and potential therapeutic targeting in diverse human cancers.
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