Construction of therapeutically relevant human prostate epithelial fate map by utilising miRNA and mRNA microarray expression data

Jayant K Rane; Antti Ylipää; Rachel Adamson; Vincent M Mann; Matthew S Simms; Anne T Collins; Tapio Visakorpi; Matti Nykter; Norman J Maitland

doi:10.1038/bjc.2015.262

Construction of therapeutically relevant human prostate epithelial fate map by utilising miRNA and mRNA microarray expression data

Jayant K Rane, Antti Ylipää, Rachel Adamson, Vincent M Mann, Matthew S Simms, Anne T Collins, Tapio Visakorpi, Matti Nykter, Norman J Maitland

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Objective identification of key miRNAs from transcriptomic data is difficult owing to the inherent inconsistencies within miRNA target-prediction algorithms and the promiscuous nature of miRNA-mRNA target relationship.

METHODS: An integrated database of miRNAs and their 'relevant' mRNA targets was generated from validated miRNA and mRNA microarray data sets generated from patient-derived prostate epithelial normal and cancer stem-like cells (SCs) and committed basal (CB) cells. The effect of miR-542-5p inhibition was studied to provide proof-of-principle for database utility.

RESULTS: Integration of miRNA-mRNA databases showed that signalling pathways and processes can be regulated by a single or relatively few miRNAs, for example, DNA repair/Notch pathway by miR-542-5p, P=0.008. Inhibition of miR-542-5p in CB cells (thereby achieving miR-542-5p expression levels similar to SCs) promoted efficient DNA repair and activated expression of Notch reporters, HES1 and Survivin, without inducing dedifferentiation into SCs.

CONCLUSIONS: Our novel framework impartially identifies therapeutically relevant miRNA candidates from transcriptomic data sets.British Journal of Cancer advance online publication 23 July 2015. doi:10.1038/bjc.2015.262 www.bjcancer.com.

Original language	English
Journal	British journal of cancer
Early online date	23 Jul 2015
DOIs	https://doi.org/10.1038/bjc.2015.262
Publication status	Published - 23 Jul 2015

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10.1038/bjc.2015.262

Cite this

@article{96f170ed679f466e99d480439e4f573a,

title = "Construction of therapeutically relevant human prostate epithelial fate map by utilising miRNA and mRNA microarray expression data",

abstract = "BACKGROUND: Objective identification of key miRNAs from transcriptomic data is difficult owing to the inherent inconsistencies within miRNA target-prediction algorithms and the promiscuous nature of miRNA-mRNA target relationship.METHODS: An integrated database of miRNAs and their 'relevant' mRNA targets was generated from validated miRNA and mRNA microarray data sets generated from patient-derived prostate epithelial normal and cancer stem-like cells (SCs) and committed basal (CB) cells. The effect of miR-542-5p inhibition was studied to provide proof-of-principle for database utility.RESULTS: Integration of miRNA-mRNA databases showed that signalling pathways and processes can be regulated by a single or relatively few miRNAs, for example, DNA repair/Notch pathway by miR-542-5p, P=0.008. Inhibition of miR-542-5p in CB cells (thereby achieving miR-542-5p expression levels similar to SCs) promoted efficient DNA repair and activated expression of Notch reporters, HES1 and Survivin, without inducing dedifferentiation into SCs.CONCLUSIONS: Our novel framework impartially identifies therapeutically relevant miRNA candidates from transcriptomic data sets.British Journal of Cancer advance online publication 23 July 2015. doi:10.1038/bjc.2015.262 www.bjcancer.com.",

author = "Rane, {Jayant K} and Antti Ylip{\"a}{\"a} and Rachel Adamson and Mann, {Vincent M} and Simms, {Matthew S} and Collins, {Anne T} and Tapio Visakorpi and Matti Nykter and Maitland, {Norman J}",

year = "2015",

month = jul,

day = "23",

doi = "10.1038/bjc.2015.262",

language = "English",

journal = "British journal of cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

}

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T1 - Construction of therapeutically relevant human prostate epithelial fate map by utilising miRNA and mRNA microarray expression data

AU - Rane, Jayant K

AU - Ylipää, Antti

AU - Adamson, Rachel

AU - Mann, Vincent M

AU - Simms, Matthew S

AU - Collins, Anne T

AU - Visakorpi, Tapio

AU - Nykter, Matti

AU - Maitland, Norman J

PY - 2015/7/23

Y1 - 2015/7/23

N2 - BACKGROUND: Objective identification of key miRNAs from transcriptomic data is difficult owing to the inherent inconsistencies within miRNA target-prediction algorithms and the promiscuous nature of miRNA-mRNA target relationship.METHODS: An integrated database of miRNAs and their 'relevant' mRNA targets was generated from validated miRNA and mRNA microarray data sets generated from patient-derived prostate epithelial normal and cancer stem-like cells (SCs) and committed basal (CB) cells. The effect of miR-542-5p inhibition was studied to provide proof-of-principle for database utility.RESULTS: Integration of miRNA-mRNA databases showed that signalling pathways and processes can be regulated by a single or relatively few miRNAs, for example, DNA repair/Notch pathway by miR-542-5p, P=0.008. Inhibition of miR-542-5p in CB cells (thereby achieving miR-542-5p expression levels similar to SCs) promoted efficient DNA repair and activated expression of Notch reporters, HES1 and Survivin, without inducing dedifferentiation into SCs.CONCLUSIONS: Our novel framework impartially identifies therapeutically relevant miRNA candidates from transcriptomic data sets.British Journal of Cancer advance online publication 23 July 2015. doi:10.1038/bjc.2015.262 www.bjcancer.com.

AB - BACKGROUND: Objective identification of key miRNAs from transcriptomic data is difficult owing to the inherent inconsistencies within miRNA target-prediction algorithms and the promiscuous nature of miRNA-mRNA target relationship.METHODS: An integrated database of miRNAs and their 'relevant' mRNA targets was generated from validated miRNA and mRNA microarray data sets generated from patient-derived prostate epithelial normal and cancer stem-like cells (SCs) and committed basal (CB) cells. The effect of miR-542-5p inhibition was studied to provide proof-of-principle for database utility.RESULTS: Integration of miRNA-mRNA databases showed that signalling pathways and processes can be regulated by a single or relatively few miRNAs, for example, DNA repair/Notch pathway by miR-542-5p, P=0.008. Inhibition of miR-542-5p in CB cells (thereby achieving miR-542-5p expression levels similar to SCs) promoted efficient DNA repair and activated expression of Notch reporters, HES1 and Survivin, without inducing dedifferentiation into SCs.CONCLUSIONS: Our novel framework impartially identifies therapeutically relevant miRNA candidates from transcriptomic data sets.British Journal of Cancer advance online publication 23 July 2015. doi:10.1038/bjc.2015.262 www.bjcancer.com.

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DO - 10.1038/bjc.2015.262

M3 - Article

C2 - 26203762

SN - 0007-0920

JO - British journal of cancer

JF - British journal of cancer

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