Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer Metastasis
Identifying new mechanisms that underlie the complex process of metastasis is vital to combat this fatal step in prostate cancer (PCa) progression. Small non-coding RNAs are emerging as important regulators of tumor cell biology. Here we take an integrative approach to elucidate the contribution of...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.00292/full |
| _version_ | 1811296590254571520 |
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| author | Srinivasa R. Rao Alison Howarth Patrick Kratschmer Ann E. Snaith Clarence Yapp Daniel Ebner Freddie C. Hamdy Claire M. Edwards Claire M. Edwards |
| author_facet | Srinivasa R. Rao Alison Howarth Patrick Kratschmer Ann E. Snaith Clarence Yapp Daniel Ebner Freddie C. Hamdy Claire M. Edwards Claire M. Edwards |
| author_sort | Srinivasa R. Rao |
| collection | DOAJ |
| description | Identifying new mechanisms that underlie the complex process of metastasis is vital to combat this fatal step in prostate cancer (PCa) progression. Small non-coding RNAs are emerging as important regulators of tumor cell biology. Here we take an integrative approach to elucidate the contribution of microRNAs to metastatic progression, combining transcriptomic analysis with functional screens for migration and morphology. We developed high-content microscopy, high-throughput functional screens for migration and morphology in PCa cells using a microRNA library. RNA-Seq analysis of paired epithelial and mesenchymal PCa cells identified differential expression of 200 microRNAs. Data integration identified two microRNAs that inhibited migration, induced an epithelial-like morphology and were increased in epithelial PCa cells. An overrepresentation of the AAGUGC seed sequence was detected in all three datasets. Analysis of published datasets of patients with PCa identified microRNAs of clinical relevance. The integration of high-throughput functional and expression analyses identifies microRNAs with clinical significance that modulate metastatic behavior in PCa. |
| first_indexed | 2024-04-13T05:50:42Z |
| format | Article |
| id | doaj.art-c186622b7f404a8b9206592704de88ba |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T05:50:42Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-c186622b7f404a8b9206592704de88ba2022-12-22T02:59:47ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-03-011010.3389/fonc.2020.00292512215Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer MetastasisSrinivasa R. Rao0Alison Howarth1Patrick Kratschmer2Ann E. Snaith3Clarence Yapp4Daniel Ebner5Freddie C. Hamdy6Claire M. Edwards7Claire M. Edwards8Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United KingdomNuffield Department of Medicine, Target Discovery Institute, University of Oxford, Oxford, United KingdomNuffield Department of Surgical Sciences, University of Oxford, Oxford, United KingdomNuffield Department of Surgical Sciences, University of Oxford, Oxford, United KingdomNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, United KingdomNuffield Department of Medicine, Target Discovery Institute, University of Oxford, Oxford, United KingdomNuffield Department of Surgical Sciences, University of Oxford, Oxford, United KingdomNuffield Department of Surgical Sciences, University of Oxford, Oxford, United KingdomNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, United KingdomIdentifying new mechanisms that underlie the complex process of metastasis is vital to combat this fatal step in prostate cancer (PCa) progression. Small non-coding RNAs are emerging as important regulators of tumor cell biology. Here we take an integrative approach to elucidate the contribution of microRNAs to metastatic progression, combining transcriptomic analysis with functional screens for migration and morphology. We developed high-content microscopy, high-throughput functional screens for migration and morphology in PCa cells using a microRNA library. RNA-Seq analysis of paired epithelial and mesenchymal PCa cells identified differential expression of 200 microRNAs. Data integration identified two microRNAs that inhibited migration, induced an epithelial-like morphology and were increased in epithelial PCa cells. An overrepresentation of the AAGUGC seed sequence was detected in all three datasets. Analysis of published datasets of patients with PCa identified microRNAs of clinical relevance. The integration of high-throughput functional and expression analyses identifies microRNAs with clinical significance that modulate metastatic behavior in PCa.https://www.frontiersin.org/article/10.3389/fonc.2020.00292/fullmicroRNAprostate cancerscreeningEMT - epithelial to mesenchymal transitionmorphological analysismigration screening |
| spellingShingle | Srinivasa R. Rao Alison Howarth Patrick Kratschmer Ann E. Snaith Clarence Yapp Daniel Ebner Freddie C. Hamdy Claire M. Edwards Claire M. Edwards Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer Metastasis Frontiers in Oncology microRNA prostate cancer screening EMT - epithelial to mesenchymal transition morphological analysis migration screening |
| title | Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer Metastasis |
| title_full | Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer Metastasis |
| title_fullStr | Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer Metastasis |
| title_full_unstemmed | Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer Metastasis |
| title_short | Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer Metastasis |
| title_sort | transcriptomic and functional screens reveal micrornas that modulate prostate cancer metastasis |
| topic | microRNA prostate cancer screening EMT - epithelial to mesenchymal transition morphological analysis migration screening |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.00292/full |
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