miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors

Espen Enerly, Israel Steinfeld, Kristine Kleivi, Suvi-Katri Leivonen, Miriam R. Aure, Hege G. Russnes, Jo Anders Rønneberg, Hilde Johnsen, Roy Navon, Einar Rødland, Rami Mäkelä, Bjørn Naume, Merja Perälä, Olli Kallioniemi, Vessela N. Kristensen, Zohar Yakhini (Corresponding Author), Anne-Lise Børresen-Dale (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

222 Citations (Scopus)

Abstract

Introduction: Few studies have performed expression profiling of both miRNA and mRNA from the same primary breast carcinomas. In this study we present and analyze data derived from expression profiling of 799 miRNAs in 101 primary human breast tumors, along with genome-wide mRNA profiles and extensive clinical information. Methods: We investigate the relationship between these molecular components, in terms of their correlation with each other and with clinical characteristics. We use a systems biology approach to examine the correlative relationship between miRNA and mRNAs using statistical enrichment methods. Results: We identify statistical significant differential expression of miRNAs between molecular intrinsic subtypes, and between samples with different levels of proliferation. Specifically, we point to miRNAs significantly associated with TP53 and ER status. We also show that several cellular processes, such as proliferation, cell adhesion and immune response, are strongly associated with certain miRNAs. We validate the role of miRNAs in regulating proliferation using high-throughput lysate-microarrays on cell lines and point to potential drivers of this process. Conclusion: This study provides a comprehensive dataset as well as methods and system-level results that jointly form a basis for further work on understanding the role of miRNA in primary breast cancer.
Original languageEnglish
Article numbere16915
JournalPLoS ONE
Volume6
Issue number2
DOIs
Publication statusPublished - 2011
MoE publication typeA1 Journal article-refereed

Fingerprint

MicroRNAs
microRNA
breast neoplasms
Tumors
Breast Neoplasms
Messenger RNA
cell adhesion
methodology
cell lines
immune response
Biological Sciences
genome
Systems Biology
Cell adhesion
Microarrays
Cell Adhesion
sampling
Genes
Cells
Throughput

Keywords

  • breast cancer
  • cancer
  • microRNA

Cite this

Enerly, E., Steinfeld, I., Kleivi, K., Leivonen, S-K., Aure, M. R., Russnes, H. G., ... Børresen-Dale, A-L. (2011). miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors. PLoS ONE, 6(2), [e16915]. https://doi.org/10.1371/journal.pone.0016915
Enerly, Espen ; Steinfeld, Israel ; Kleivi, Kristine ; Leivonen, Suvi-Katri ; Aure, Miriam R. ; Russnes, Hege G. ; Rønneberg, Jo Anders ; Johnsen, Hilde ; Navon, Roy ; Rødland, Einar ; Mäkelä, Rami ; Naume, Bjørn ; Perälä, Merja ; Kallioniemi, Olli ; Kristensen, Vessela N. ; Yakhini, Zohar ; Børresen-Dale, Anne-Lise. / miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors. In: PLoS ONE. 2011 ; Vol. 6, No. 2.
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title = "miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors",
abstract = "Introduction: Few studies have performed expression profiling of both miRNA and mRNA from the same primary breast carcinomas. In this study we present and analyze data derived from expression profiling of 799 miRNAs in 101 primary human breast tumors, along with genome-wide mRNA profiles and extensive clinical information. Methods: We investigate the relationship between these molecular components, in terms of their correlation with each other and with clinical characteristics. We use a systems biology approach to examine the correlative relationship between miRNA and mRNAs using statistical enrichment methods. Results: We identify statistical significant differential expression of miRNAs between molecular intrinsic subtypes, and between samples with different levels of proliferation. Specifically, we point to miRNAs significantly associated with TP53 and ER status. We also show that several cellular processes, such as proliferation, cell adhesion and immune response, are strongly associated with certain miRNAs. We validate the role of miRNAs in regulating proliferation using high-throughput lysate-microarrays on cell lines and point to potential drivers of this process. Conclusion: This study provides a comprehensive dataset as well as methods and system-level results that jointly form a basis for further work on understanding the role of miRNA in primary breast cancer.",
keywords = "breast cancer, cancer, microRNA",
author = "Espen Enerly and Israel Steinfeld and Kristine Kleivi and Suvi-Katri Leivonen and Aure, {Miriam R.} and Russnes, {Hege G.} and R{\o}nneberg, {Jo Anders} and Hilde Johnsen and Roy Navon and Einar R{\o}dland and Rami M{\"a}kel{\"a} and Bj{\o}rn Naume and Merja Per{\"a}l{\"a} and Olli Kallioniemi and Kristensen, {Vessela N.} and Zohar Yakhini and Anne-Lise B{\o}rresen-Dale",
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Enerly, E, Steinfeld, I, Kleivi, K, Leivonen, S-K, Aure, MR, Russnes, HG, Rønneberg, JA, Johnsen, H, Navon, R, Rødland, E, Mäkelä, R, Naume, B, Perälä, M, Kallioniemi, O, Kristensen, VN, Yakhini, Z & Børresen-Dale, A-L 2011, 'miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors', PLoS ONE, vol. 6, no. 2, e16915. https://doi.org/10.1371/journal.pone.0016915

miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors. / Enerly, Espen; Steinfeld, Israel; Kleivi, Kristine; Leivonen, Suvi-Katri; Aure, Miriam R.; Russnes, Hege G.; Rønneberg, Jo Anders; Johnsen, Hilde; Navon, Roy; Rødland, Einar; Mäkelä, Rami; Naume, Bjørn; Perälä, Merja; Kallioniemi, Olli; Kristensen, Vessela N.; Yakhini, Zohar (Corresponding Author); Børresen-Dale, Anne-Lise (Corresponding Author).

In: PLoS ONE, Vol. 6, No. 2, e16915, 2011.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors

AU - Enerly, Espen

AU - Steinfeld, Israel

AU - Kleivi, Kristine

AU - Leivonen, Suvi-Katri

AU - Aure, Miriam R.

AU - Russnes, Hege G.

AU - Rønneberg, Jo Anders

AU - Johnsen, Hilde

AU - Navon, Roy

AU - Rødland, Einar

AU - Mäkelä, Rami

AU - Naume, Bjørn

AU - Perälä, Merja

AU - Kallioniemi, Olli

AU - Kristensen, Vessela N.

AU - Yakhini, Zohar

AU - Børresen-Dale, Anne-Lise

PY - 2011

Y1 - 2011

N2 - Introduction: Few studies have performed expression profiling of both miRNA and mRNA from the same primary breast carcinomas. In this study we present and analyze data derived from expression profiling of 799 miRNAs in 101 primary human breast tumors, along with genome-wide mRNA profiles and extensive clinical information. Methods: We investigate the relationship between these molecular components, in terms of their correlation with each other and with clinical characteristics. We use a systems biology approach to examine the correlative relationship between miRNA and mRNAs using statistical enrichment methods. Results: We identify statistical significant differential expression of miRNAs between molecular intrinsic subtypes, and between samples with different levels of proliferation. Specifically, we point to miRNAs significantly associated with TP53 and ER status. We also show that several cellular processes, such as proliferation, cell adhesion and immune response, are strongly associated with certain miRNAs. We validate the role of miRNAs in regulating proliferation using high-throughput lysate-microarrays on cell lines and point to potential drivers of this process. Conclusion: This study provides a comprehensive dataset as well as methods and system-level results that jointly form a basis for further work on understanding the role of miRNA in primary breast cancer.

AB - Introduction: Few studies have performed expression profiling of both miRNA and mRNA from the same primary breast carcinomas. In this study we present and analyze data derived from expression profiling of 799 miRNAs in 101 primary human breast tumors, along with genome-wide mRNA profiles and extensive clinical information. Methods: We investigate the relationship between these molecular components, in terms of their correlation with each other and with clinical characteristics. We use a systems biology approach to examine the correlative relationship between miRNA and mRNAs using statistical enrichment methods. Results: We identify statistical significant differential expression of miRNAs between molecular intrinsic subtypes, and between samples with different levels of proliferation. Specifically, we point to miRNAs significantly associated with TP53 and ER status. We also show that several cellular processes, such as proliferation, cell adhesion and immune response, are strongly associated with certain miRNAs. We validate the role of miRNAs in regulating proliferation using high-throughput lysate-microarrays on cell lines and point to potential drivers of this process. Conclusion: This study provides a comprehensive dataset as well as methods and system-level results that jointly form a basis for further work on understanding the role of miRNA in primary breast cancer.

KW - breast cancer

KW - cancer

KW - microRNA

UR - http://doi.org/10.1371/annotation/a20454a7-ddc4-4657-b73c-185bd6ec6977

U2 - 10.1371/journal.pone.0016915

DO - 10.1371/journal.pone.0016915

M3 - Article

VL - 6

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 2

M1 - e16915

ER -

Enerly E, Steinfeld I, Kleivi K, Leivonen S-K, Aure MR, Russnes HG et al. miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors. PLoS ONE. 2011;6(2). e16915. https://doi.org/10.1371/journal.pone.0016915