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Published on: November 19, 2019
Profile of chimeric RNAs and TMPRSS2-ERG e2e4 isoform in neuroendocrine prostate cancer
Qiong Wang1,2,3, Junxiu Chen1,4, Sandeep Singh2
1Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Purpose:
Specific gene fusions and their fusion products (chimeric RNA and protein) have served as ideal diagnostic markers and therapeutic targets for cancer. However, few systematic studies for chimeric RNAs have been conducted in neuroendocrine prostate cancer (NEPC). In this study, we explored the landscape of chimeric RNAs in different types of prostate cancer (PCa) cell lines and aimed to identify chimeric RNAs specifically expressed in NEPC.
Methods:
To do so, we employed the RNA-seq data of eight prostate related cell lines from Cancer Cell Line Encyclopedia (CCLE) for chimeric RNA identification. Multiple filtering criteria were used and the candidate chimeric RNAs were characterized at multiple levels and from various angles. We then performed experimental validation on all 80 candidates, and focused on the ones that are specific to NEPC. Lastly, we studied the clinical relevance and effect of one chimera in neuroendocrine process.
Results:
Out of 80 candidates, 15 were confirmed to be expressed preferentially in NEPC lines. Among them, 13 of the 15 were found to be specifically expressed in NEPC, and four were further validated in another NEPC cell line. Importantly, in silico analysis showed that tumor malignancy may be correlated to the level of these chimeric RNAs. Clinically, the expression of TMPRSS2-ERG (e2e4) was elevated in tumor tissues and indicated poor clinical prognosis, whereas the parental wild type transcripts had no such association. Furthermore, compared to the most frequently detected TMPRSS2-ERG form (e1e4), e2e4 encodes 31 more amino acids and accelerated neuroendocrine process of prostate cancer.
Conclusions:
In summary, these findings painted the landscape of chimeric RNA in NEPC and supported the idea that some chimeric RNAs may represent additional biomarkers and/or treatment targets independent of parental gene transcripts.
Insights
Researchers identified novel chimeric RNAs specific to neuroendocrine prostate cancer (NEPC). These findings highlight potential new biomarkers and therapeutic targets for NEPC, distinct from their parent genes.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Chimeric RNAs are valuable cancer biomarkers and therapeutic targets.
- Systematic studies of chimeric RNAs in neuroendocrine prostate cancer (NEPC) are limited.
Purpose of the Study:
- To explore the landscape of chimeric RNAs in various prostate cancer (PCa) cell lines.
- To identify chimeric RNAs specifically expressed in NEPC.
Main Methods:
- Utilized RNA-sequencing data from eight PCa cell lines (Cancer Cell Line Encyclopedia).
- Applied multiple filtering criteria for chimeric RNA identification and characterization.
- Performed experimental validation and focused on NEPC-specific candidates.
- Investigated clinical relevance and functional impact of identified chimeras.
Main Results:
- Identified 80 candidate chimeric RNAs, with 15 preferentially expressed in NEPC lines.
- Confirmed 13 of these 15 chimeric RNAs were NEPC-specific, with four validated in an additional NEPC cell line.
- Found a correlation between chimeric RNA levels and tumor malignancy.
- Elevated TMPRSS2-ERG (e2e4) expression associated with poor prognosis, unlike wild-type transcripts.
- The TMPRSS2-ERG (e2e4) chimera encodes additional amino acids, accelerating NEPC progression.
Conclusions:
- Established the chimeric RNA landscape in NEPC.
- Demonstrated that certain chimeric RNAs can serve as independent biomarkers or therapeutic targets.
- Highlighted the potential of specific chimeric RNAs, like TMPRSS2-ERG (e2e4), in NEPC diagnosis and treatment.
