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...

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Main Authors: Rao, SR, Howarth, A, Kratschmer, P, Snaith, AE, Yapp, C, Ebner, D, Hamdy, FC, Edwards, CM
Format: Journal article
Language:English
Published: Frontiers Media 2020
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author Rao, SR
Howarth, A
Kratschmer, P
Snaith, AE
Yapp, C
Ebner, D
Hamdy, FC
Edwards, CM
author_facet Rao, SR
Howarth, A
Kratschmer, P
Snaith, AE
Yapp, C
Ebner, D
Hamdy, FC
Edwards, CM
author_sort Rao, SR
collection OXFORD
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.
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spelling oxford-uuid:c4f4738a-94b0-4edd-a771-45f71b6c18a82022-03-27T06:27:25ZTranscriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer MetastasisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c4f4738a-94b0-4edd-a771-45f71b6c18a8EnglishSymplectic ElementsFrontiers Media 2020Rao, SRHowarth, A Kratschmer, PSnaith, AEYapp, CEbner, DHamdy, FCEdwards, CMIdentifying 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.
spellingShingle Rao, SR
Howarth, A
Kratschmer, P
Snaith, AE
Yapp, C
Ebner, D
Hamdy, FC
Edwards, CM
Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer Metastasis
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
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