Androgen-Driven Fusion Genes and Chimeric Transcripts in Prostate Cancer
Androgens are steroid hormones governing the male reproductive development and function. As such, androgens and the key mediator of their effects, androgen receptor (AR), have a leading role in many diseases. Prostate cancer is a major disease where AR and its transcription factor function affect a...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-02-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.623809/full |
| _version_ | 1818353357073416192 |
|---|---|
| author | Mauro Scaravilli Sonja Koivukoski Leena Latonen |
| author_facet | Mauro Scaravilli Sonja Koivukoski Leena Latonen |
| author_sort | Mauro Scaravilli |
| collection | DOAJ |
| description | Androgens are steroid hormones governing the male reproductive development and function. As such, androgens and the key mediator of their effects, androgen receptor (AR), have a leading role in many diseases. Prostate cancer is a major disease where AR and its transcription factor function affect a significant number of patients worldwide. While disease-related AR-driven transcriptional programs are connected to the presence and activity of the receptor itself, also novel modes of transcriptional regulation by androgens are exploited by cancer cells. One of the most intriguing and ingenious mechanisms is to bring previously unconnected genes under the control of AR. Most often this occurs through genetic rearrangements resulting in fusion genes where an androgen-regulated promoter area is combined to a protein-coding area of a previously androgen-unaffected gene. These gene fusions are distinctly frequent in prostate cancer compared to other common solid tumors, a phenomenon still requiring an explanation. Interestingly, also another mode of connecting androgen regulation to a previously unaffected gene product exists via transcriptional read-through mechanisms. Furthermore, androgen regulation of fusion genes and transcripts is not linked to only protein-coding genes. Pseudogenes and non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) can also be affected by androgens and de novo functions produced. In this review, we discuss the prevalence, molecular mechanisms, and functional evidence for androgen-regulated prostate cancer fusion genes and transcripts. We also discuss the clinical relevance of especially the most common prostate cancer fusion gene TMPRSS2-ERG, as well as present open questions of prostate cancer fusions requiring further investigation. |
| first_indexed | 2024-12-13T19:08:14Z |
| format | Article |
| id | doaj.art-e69a2649073540a0b3e48d4ec3619c9a |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-13T19:08:14Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-e69a2649073540a0b3e48d4ec3619c9a2022-12-21T23:34:29ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-02-01910.3389/fcell.2021.623809623809Androgen-Driven Fusion Genes and Chimeric Transcripts in Prostate CancerMauro ScaravilliSonja KoivukoskiLeena LatonenAndrogens are steroid hormones governing the male reproductive development and function. As such, androgens and the key mediator of their effects, androgen receptor (AR), have a leading role in many diseases. Prostate cancer is a major disease where AR and its transcription factor function affect a significant number of patients worldwide. While disease-related AR-driven transcriptional programs are connected to the presence and activity of the receptor itself, also novel modes of transcriptional regulation by androgens are exploited by cancer cells. One of the most intriguing and ingenious mechanisms is to bring previously unconnected genes under the control of AR. Most often this occurs through genetic rearrangements resulting in fusion genes where an androgen-regulated promoter area is combined to a protein-coding area of a previously androgen-unaffected gene. These gene fusions are distinctly frequent in prostate cancer compared to other common solid tumors, a phenomenon still requiring an explanation. Interestingly, also another mode of connecting androgen regulation to a previously unaffected gene product exists via transcriptional read-through mechanisms. Furthermore, androgen regulation of fusion genes and transcripts is not linked to only protein-coding genes. Pseudogenes and non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) can also be affected by androgens and de novo functions produced. In this review, we discuss the prevalence, molecular mechanisms, and functional evidence for androgen-regulated prostate cancer fusion genes and transcripts. We also discuss the clinical relevance of especially the most common prostate cancer fusion gene TMPRSS2-ERG, as well as present open questions of prostate cancer fusions requiring further investigation.https://www.frontiersin.org/articles/10.3389/fcell.2021.623809/fullandrogen receptorandrogensprostate cancerfusion genefusion transcriptcastration-resistant prostate cancer |
| spellingShingle | Mauro Scaravilli Sonja Koivukoski Leena Latonen Androgen-Driven Fusion Genes and Chimeric Transcripts in Prostate Cancer Frontiers in Cell and Developmental Biology androgen receptor androgens prostate cancer fusion gene fusion transcript castration-resistant prostate cancer |
| title | Androgen-Driven Fusion Genes and Chimeric Transcripts in Prostate Cancer |
| title_full | Androgen-Driven Fusion Genes and Chimeric Transcripts in Prostate Cancer |
| title_fullStr | Androgen-Driven Fusion Genes and Chimeric Transcripts in Prostate Cancer |
| title_full_unstemmed | Androgen-Driven Fusion Genes and Chimeric Transcripts in Prostate Cancer |
| title_short | Androgen-Driven Fusion Genes and Chimeric Transcripts in Prostate Cancer |
| title_sort | androgen driven fusion genes and chimeric transcripts in prostate cancer |
| topic | androgen receptor androgens prostate cancer fusion gene fusion transcript castration-resistant prostate cancer |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.623809/full |
| work_keys_str_mv | AT mauroscaravilli androgendrivenfusiongenesandchimerictranscriptsinprostatecancer AT sonjakoivukoski androgendrivenfusiongenesandchimerictranscriptsinprostatecancer AT leenalatonen androgendrivenfusiongenesandchimerictranscriptsinprostatecancer |