A variant of the KLK4 gene is expressed as a cis sense-antisense chimeric transcript in prostate cancer cells
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Description
In humans, more than 30,000 chimeric transcripts originating from 23,686 genes have been identified. The mechanisms and association of chimeric transcripts arising from chromosomal rearrangements with cancer are well established, but much remains unknown regarding the biogenesis and importance of other chimeric transcripts that arise from nongenomic alterations. Recently, a SLC45A3–ELK4 chimera has been shown to be androgen-regulated, and is overexpressed in metastatic or high-grade prostate tumors relative to local prostate cancers. Here, we characterize the expression of a KLK4 cis sense–antisense chimeric transcript, and show other examples in prostate cancer. Using non-protein-coding microarray analyses, we initially identified an androgen-regulated antisense transcript within the 3′ untranslated region of the KLK4 gene in LNCaP cells. The KLK4 cis-NAT was validated by strand-specific linker-mediated RT-PCR and Northern blotting. Characterization of the KLK4 cis-NAT by 5′ and 3′ rapid amplification of cDNA ends (RACE) revealed that this transcript forms multiple fusions with the KLK4 sense transcript. Lack of KLK4 antisense promoter activity using reporter assays suggests that these transcripts are unlikely to arise from a trans-splicing mechanism. 5′ RACE and analyses of deep sequencing data from LNCaP cells treated ±androgens revealed six high-confidence sense–antisense chimeras of which three were supported by the cDNA databases. In this study, we have shown complex gene expression at the KLK4 locus that might be a hallmark of cis sense–antisense chimeric transcription.
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ID Code: | 42672 | ||||||
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Item Type: | Contribution to Journal (Journal Article) | ||||||
Refereed: | Yes | ||||||
ORCID iD: |
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Measurements or Duration: | 11 pages | ||||||
Keywords: | Chimeric transcript, Kallikrein 4, Non coding RNA, Prostate cancer, RNA sequencing | ||||||
DOI: | 10.1261/rna.2019810 | ||||||
ISSN: | 1355-8382 | ||||||
Pure ID: | 32223888 | ||||||
Divisions: | Past > QUT Faculties & Divisions > Faculty of Health Past > QUT Faculties & Divisions > Faculty of Science and Technology Past > Institutes > Institute of Health and Biomedical Innovation |
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Funding: | |||||||
Copyright Owner: | Consult author(s) regarding copyright matters | ||||||
Copyright Statement: | This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au | ||||||
Deposited On: | 13 Jul 2011 13:05 | ||||||
Last Modified: | 02 Mar 2024 06:46 |
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