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Int. J. Mol. Sci. 2017, 18(7), 1560; doi:10.3390/ijms18071560

Co-Expression Network and Pathway Analyses Reveal Important Modules of miRNAs Regulating Milk Yield and Component Traits

1
Agriculture and Agri-Food Canada, Sherbrooke Research and Development Centre, Sherbrooke, QC J1M 0C8, Canada
2
Department of Animal Science, McGill University, 21111, Lakeshore Road, Ste-Anne-de Bellevue, QC H9X 3V9, Canada
3
College of Animal Science and Technology, Northwest A&F University, Xi’an 712100, China
*
Author to whom correspondence should be addressed.
Received: 22 June 2017 / Revised: 5 July 2017 / Accepted: 5 July 2017 / Published: 18 July 2017
(This article belongs to the Special Issue microRNA Regulation 2017)
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Abstract

Co-expression network analyses provide insights into the molecular interactions underlying complex traits and diseases. In this study, co-expression network analysis was performed to detect expression patterns (modules or clusters) of microRNAs (miRNAs) during lactation, and to identify miRNA regulatory mechanisms for milk yield and component traits (fat, protein, somatic cell count (SCC), lactose, and milk urea nitrogen (MUN)) via miRNA target gene enrichment analysis. miRNA expression (713 miRNAs), and milk yield and components (Fat%, Protein%, lactose, SCC, MUN) data of nine cows at each of six different time points (day 30 (D30), D70, D130, D170, D230 and D290) of an entire lactation curve were used. Four modules or clusters (GREEN, BLUE, RED and TURQUOISE) of miRNAs were identified as important for milk yield and component traits. The GREEN and BLUE modules were significantly correlated (|r| > 0.5) with milk yield and lactose, respectively. The RED and TURQUOISE modules were significantly correlated (|r| > 0.5) with both SCC and lactose. In the GREEN module, three abundantly expressed miRNAs (miR-148a, miR-186 and miR-200a) were most significantly correlated to milk yield, and are probably the most important miRNAs for this trait. DDR1 and DDHX1 are hub genes for miRNA regulatory networks controlling milk yield, while HHEX is an important transcription regulator for these networks. miR-18a, miR-221/222 cluster, and transcription factors HOXA7, and NOTCH 3 and 4, are important for the regulation of lactose. miR-142, miR-146a, and miR-EIA17-14144 (a novel miRNA), and transcription factors in the SMAD family and MYB, are important for the regulation of SCC. Important signaling pathways enriched for target genes of miRNAs of significant modules, included protein kinase A and PTEN signaling for milk yield, eNOS and Noth signaling for lactose, and TGF β, HIPPO, Wnt/β-catenin and cell cycle signaling for SCC. Relevant enriched gene ontology (GO)-terms related to milk and mammary gland traits included cell differentiation, G-protein coupled receptor activity, and intracellular signaling transduction. Overall, this study uncovered regulatory networks in which miRNAs interacted with each other to regulate lactation traits. View Full-Text
Keywords: co-expression network; dairy cows; hub genes; lactation; microRNA; signaling pathways; transcription factors. co-expression network; dairy cows; hub genes; lactation; microRNA; signaling pathways; transcription factors.
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Do, D.N.; Dudemaine, P.-L.; Li, R.; Ibeagha-Awemu, E.M. Co-Expression Network and Pathway Analyses Reveal Important Modules of miRNAs Regulating Milk Yield and Component Traits. Int. J. Mol. Sci. 2017, 18, 1560.

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