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Updated: Feb 3, 2026
Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
Published on: June 24, 2021
Characterization of kinase gene expression and splicing profile in prostate cancer with RNA-Seq data
Huijuan Feng1,2, Tingting Li3, Xuegong Zhang4,5
1MOE Key Laboratory of Bioinformatics, Division of Bioinformatics and Center for Synthetic and Systems Biology, TNLIST, Department of Automation, Tsinghua University, Beijing, 100084, China.
Background:
Alternative splicing is a ubiquitous post-transcriptional regulation mechanism in most eukaryotic genes. Aberrant splicing isoforms and abnormal isoform ratios can contribute to cancer development. Kinase genes are key regulators of multiple cellular processes. Many kinases are found to be oncogenic and have been intensively investigated in the study of cancer and drugs. RNA-Seq provides a powerful technology for genome-wide study of alternative splicing in cancer besides the conventional gene expression profiling. But this potential has not been fully demonstrated yet.
Methods:
We characterized the transcriptome profile of prostate cancer using RNA-Seq data from viewpoints of both differential expression and differential splicing, with an emphasis on kinase genes and their splicing variations. We built a pipeline to conduct differential expression and differential splicing analysis, followed by functional enrichment analysis. We performed kinase domain analysis to identify the functionally important candidate kinase gene in prostate cancer, and calculated the expression levels of isoforms to explore the function of isoform switching of kinase genes in prostate cancer.
Results:
We identified distinct gene groups from differential expression and splicing analyses, which suggested that alternative splicing adds another level to gene expression regulation. Enriched GO terms of differentially expressed and spliced kinase genes were found to play different roles in regulation of cellular metabolism. Function analysis on differentially spliced kinase genes showed that differentially spliced exons of these genes are significantly enriched in protein kinase domains. Among them, we found that gene CDK5 has isoform switching between prostate cancer and benign tissues, which may affect cancer development by changing androgen receptor (AR) phosphorylation. The observation was validated in another RNA-Seq dataset of prostate cancer cell lines.
Conclusions:
Our work characterized the expression and splicing profiles of kinase genes in prostate cancer and proposed a hypothetical model on isoform switching of CDK5 and AR phosphorylation in prostate cancer. These findings bring new understanding to the role of alternatively spliced kinases in prostate cancer and also demonstrate the use of RNA-Seq data in studying alternative splicing in cancer.
Insights
Alternative splicing of kinase genes plays a role in prostate cancer. RNA-Seq analysis revealed specific splicing variations in CDK5, potentially impacting androgen receptor phosphorylation and cancer development.
Area of Science:
- Genomics
- Molecular Biology
- Cancer Research
Background:
- Alternative splicing is a key post-transcriptional regulation mechanism.
- Aberrant splicing and altered isoform ratios contribute to cancer.
- Kinase genes are crucial regulators, with many implicated as oncogenes.
Purpose of the Study:
- To characterize the transcriptome profile of prostate cancer focusing on kinase gene expression and splicing.
- To investigate the role of alternative splicing in kinase genes within prostate cancer.
- To demonstrate the utility of RNA-Seq for studying alternative splicing in cancer.
Main Methods:
- Utilized RNA-Seq data for differential expression and differential splicing analysis of prostate cancer transcriptomes.
- Developed a bioinformatics pipeline for comprehensive analysis.
- Performed kinase domain analysis and isoform expression quantification.
Main Results:
- Identified distinct gene groups through differential expression and splicing analyses.
- Differentially spliced kinase genes showed enrichment in protein kinase domains.
- Observed isoform switching in CDK5 between prostate and benign tissues, potentially affecting androgen receptor phosphorylation.
Conclusions:
- Characterized kinase gene expression and splicing profiles in prostate cancer.
- Proposed a model for CDK5 isoform switching and its effect on androgen receptor phosphorylation.
- Highlighted the significance of alternative splicing in kinase genes for prostate cancer development.
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