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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
Transcription-mediated chimeric RNAs in prostate cancer: time to revisit old hypothesis?
Guoping Ren1, Yanling Zhang, Xueying Mao
11 Department of Pathology, The First Affiliated Hospital, Zhejiang University Medical College , Hangzhou, China .
Abstract:
Chromosomal rearrangements and fusion genes play important roles in tumor development and progression. Four high-frequency prostate cancer-specific fusion genes were recently reported in Chinese cases. We attempted to confirm one of the fusion genes, USP9Y-TTTY15, by reverse transcription PCR, but detected the presence of the USP9Y-TTTY15 fusion transcript in cancer samples, nonmalignant prostate tissues, and normal tissues from other organs, demonstrating that it is a transcription-induced chimeric RNA, which is commonly produced in normal tissues. In 105 prostate cancer samples and case-matched adjacent nonmalignant tissues, we determined the expression level of USP9Y-TTTY15 and a previously reported transcription-induced chimeric RNA, SLC45A3-ELK4. The expression levels of both chimeric RNAs vary greatly in cancer and normal cells. USP9Y-TTTY15 expression is neither higher in cancer than adjacent normal tissues, nor correlated with features of advanced prostate cancer. Although the expression level of SLC45A3-ELK4 is higher in cancer than normal cells, and a dramatic increase in its expression from normal to cancer cells is correlated with advanced disease, its expression level in cancer samples alone is not correlated with any clinical parameters. These data show that both chimeric RNAs contribute less to prostate carcinogenesis than previously reported.
Insights
Two prostate cancer chimeric RNAs, USP9Y-TTTY15 and SLC45A3-ELK4, are commonly found in normal tissues. Their expression levels do not strongly correlate with prostate cancer development or progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chromosomal rearrangements and fusion genes are implicated in cancer development.
- Previous studies reported high-frequency prostate cancer-specific fusion genes in Chinese populations.
- The role of specific chimeric RNAs in prostate cancer requires further investigation.
Purpose of the Study:
- To validate the presence and significance of the USP9Y-TTTY15 fusion gene in prostate cancer.
- To assess the expression levels of USP9Y-TTTY15 and SLC45A3-ELK4 in prostate cancer and nonmalignant tissues.
- To determine the correlation between these chimeric RNAs and prostate cancer progression.
Main Methods:
- Reverse transcription PCR (RT-PCR) was used to detect fusion transcripts.
- Expression levels of USP9Y-TTTY15 and SLC45A3-ELK4 were quantified in 105 prostate cancer samples and matched adjacent nonmalignant tissues.
- Statistical analysis was performed to correlate expression with clinical parameters and disease stage.
Main Results:
- USP9Y-TTTY15 was detected in cancer, nonmalignant prostate, and normal tissues, indicating it is a common transcription-induced chimeric RNA.
- USP9Y-TTTY15 expression was not significantly higher in cancer than normal tissues and did not correlate with advanced prostate cancer.
- SLC45A3-ELK4 expression was higher in cancer than normal tissues and correlated with disease advancement, but not with specific clinical parameters within cancer samples.
Conclusions:
- USP9Y-TTTY15 is a transcription-induced chimeric RNA not specific to prostate cancer and likely plays a minimal role in its carcinogenesis.
- While SLC45A3-ELK4 shows increased expression in cancer and correlates with advancement, its overall contribution to prostate carcinogenesis appears less significant than previously suggested.
- These findings suggest that the previously reported high-frequency prostate cancer-specific fusion genes may be transcription-induced chimeric RNAs with limited oncogenic roles.
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