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Moss TJ, Luo Z, Seviour EG, et al. Genome-wide perturbations by miRNAs map onto functional cellular pathways, identifying regulators of chromatin modifiers. NPJ Syst Biol Appl. 2015;1:15001doi: 10.1038/npjsba.2015.1.
Moss, T. J., Luo, Z., Seviour, E. G., Sehgal, V., Lu, Y., Hill, S. M., Rupaimoole, R., Lee, J. S., Rodriguez-Aguayo, C., Lopez-Berestein, G., Sood, A. K., Azencott, R., Gray, J. W., Mukherjee, S., Mills, G. B., & Ram, P. T. (2015). Genome-wide perturbations by miRNAs map onto functional cellular pathways, identifying regulators of chromatin modifiers. NPJ systems biology and applications, 115001. https://doi.org/10.1038/npjsba.2015.1
Moss, Tyler J, et al. "Genome-wide perturbations by miRNAs map onto functional cellular pathways, identifying regulators of chromatin modifiers." NPJ systems biology and applications vol. 1 (2015): 15001. doi: https://doi.org/10.1038/npjsba.2015.1
Moss TJ, Luo Z, Seviour EG, Sehgal V, Lu Y, Hill SM, Rupaimoole R, Lee JS, Rodriguez-Aguayo C, Lopez-Berestein G, Sood AK, Azencott R, Gray JW, Mukherjee S, Mills GB, Ram PT. Genome-wide perturbations by miRNAs map onto functional cellular pathways, identifying regulators of chromatin modifiers. NPJ Syst Biol Appl. 2015 Sep 28;1:15001. doi: 10.1038/npjsba.2015.1. eCollection 2015. PMID: 28725457; PMCID: PMC5516802.
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NPJ Syst Biol Appl. 2015 Sep 28;1:15001. doi: 10.1038/npjsba.2015.1. eCollection 2015.

Genome-wide perturbations by miRNAs map onto functional cellular pathways, identifying regulators of chromatin modifiers.

NPJ systems biology and applications

Tyler J Moss, Zijun Luo, Elena G Seviour, Vasudha Sehgal, Yiling Lu, Steven M Hill, Rajesha Rupaimoole, Ju-Seog Lee, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Anil K Sood, Robert Azencott, Joe W Gray, Sach Mukherjee, Gordon B Mills, Prahlad T Ram

Affiliations

  1. Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  2. Medical Research Council Biostatistics Unit, Cambridge, UK.
  3. Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  4. Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  5. Center for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  6. Department of Mathematics, University of Houston, Houston, TX, USA.
  7. Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA.
  8. Cancer Research UK Cambridge Institute, School of Clinical Medicine, University of Cambridge, Robinson Way, Cambridge, UK.

PMID: 28725457 PMCID: PMC5516802 DOI: 10.1038/npjsba.2015.1

Abstract

BACKGROUND: Regulation of gene expression by microRNAs (miRNAs) is critical for determining cellular fate and function. Dysregulation of miRNA expression contributes to the development and progression of multiple diseases. miRNA can target multiple mRNAs, making deconvolution of the effects of miRNA challenging and the complexity of regulation of cellular pathways by miRNAs at the functional protein level remains to be elucidated. Therefore, we sought to determine the effects of expression of miRNAs in breast and ovarian cancer cells on cellular pathways by measuring systems-wide miRNA perturbations to protein and phosphoproteins.

METHODS: We measure protein level changes by reverse-phase protein array (RPPA) in MDA-MB-231, SKOV3.ip1 and HEYA8 cancer cell lines transfected by a library of 879 human miRNA mimics.

RESULTS: The effects of multiple miRNAs-protein networks converged in five broad functional clusters of miRNA, suggesting a broad overlap of miRNA action on cellular pathways. Detailed analysis of miRNA clusters revealed novel miRNA/cell cycle protein networks, which we functionally validated.

CONCLUSIONS: Mapping of miRNA-induced protein and phosphoprotein changes onto pathways revealed new miRNA-cellular pathway connectivity, paving the way for targeting of dysregulated pathways with potential miRNA-based therapeutics.

Conflict of interest statement

The authors declare no conflict of interest.

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