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Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
Published on: July 22, 2020
Bioinformatics analysis of SRSF1-controlled gene networks in colorectal cancer
Junxiu Sheng1,2, Jinyao Zhao2, Qiuhong Xu2
1Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
Abstract:
Colorectal cancer is the third most common type of cancer and the fourth leading cause of cancer-associated mortality worldwide. Serine/arginine-rich splicing factor 1 (SRSF1) is a well-characterized oncogenic factor that promotes tumorigenesis by controlling a number of alternative splicing events. However, there is limited network analysis, from a global aspect, to study the effect of SRSF1 on colorectal cancer. In the present study, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of available gene regulation data from The Cancer Genome Atlas database revealed the enriched functions and signaling pathways of SRSF1. Subsequently, Oncomine analysis was performed, which demonstrated that SRSF1 was upregulated in a number of types of colon cancer. From overlapping the analysis of 2,678 SRSF1-related genes and 3,625 colorectal cancer genes in GeneCards, 468 genes were identified as SRSF1-related colorectal cancer genes. The GO results revealed that these overlapped genes were primarily enriched in metabolic processes, response to DNA damage, regulation of the cell cycle and a number of additional biological processes. KEGG pathway analysis revealed that SRSF1-related colorectal cancer genes were associated with the cell cycle, deregulated signaling pathways associated with cancer progression and colorectal cancer signaling pathways. In addition, the Search Tool for the Retrieval of Interacting Genes/Proteins database and Cytoscape analysis demonstrated that 468 SRSF1-related colorectal cancer genes exhibit potential interaction networks in which these genes were enriched in DNA metabolic processes, cell cycle regulation and regulation of apoptosis. The results of the present study suggested that SRSF1 exhibited an increased degree of interaction with key molecules, including NUF2 NDC80 kinetochore complex component, kinesin family member 2C, structural maintenance of chromosomes 3, ATM serine/threonine kinase, BRCA1 DNA repair associated, protein kinase DNA-activated catalytic polypeptide, heat shock protein 90 alpha family class A member 1, ras homolog family member A, and phosphatase and tensin homolog. Collectively, the bioinformatics analysis of the present study indicated that SRSF1 may have key functions in the progression and development of colorectal cancer.
Insights
Serine/arginine-rich splicing factor 1 (SRSF1) promotes colorectal cancer by influencing gene splicing. This study identified 468 key SRSF1-related genes involved in cell cycle and DNA repair, highlighting SRSF1's role in cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Colorectal cancer is a leading cause of cancer mortality globally.
- Serine/arginine-rich splicing factor 1 (SRSF1) is an oncogenic factor promoting tumorigenesis.
- Limited network analysis exists for SRSF1's global effect on colorectal cancer.
Purpose of the Study:
- To perform a global network analysis of SRSF1's effect on colorectal cancer.
- To identify enriched functions and signaling pathways regulated by SRSF1 in colorectal cancer.
- To elucidate the molecular mechanisms underlying SRSF1's role in colorectal cancer progression.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) database for gene regulation data.
- Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.
- Integrated data from Oncomine, GeneCards, STRING, and Cytoscape for comprehensive analysis.
Main Results:
- SRSF1 was found to be upregulated in colon cancer.
- Identified 468 SRSF1-related colorectal cancer genes enriched in metabolic processes, DNA damage response, and cell cycle regulation.
- SRSF1 interacts with key molecules like NUF2, KIF2C, SMC3, ATM, and BRCA1, implicating it in DNA repair and cell cycle control.
- KEGG analysis linked these genes to cell cycle and colorectal cancer signaling pathways.
Conclusions:
- SRSF1 plays a significant role in colorectal cancer progression and development.
- SRSF1 influences critical biological processes including DNA metabolism, cell cycle regulation, and apoptosis.
- The identified SRSF1-related genes and networks provide potential therapeutic targets for colorectal cancer.

