Deciphering synergistic regulatory networks of microRNAs in hESCs and fibroblasts
Abstract
MicroRNAs (miRNAs) play crucial roles in pluripotency and differentiation of human Embryonic Stem Cells (hESCs). However, synergism among multiple miRNAs and their regulatory effects on stem cells are largely unknown. We investigated the synergistic regulations among miRNAs, which are differentially expressed in hESCs and fibroblasts (Fibs) to gain deeper insights into the regulatory mechanisms of miRNA-miRNA synergism in the differentiation of hESCs into Fibs. In this study, we identified miRNA targets incorporating differential expression profiles of miRNAs and genes in hESCs-Fibs with miRNA targeting features followed by enrichment analysis. We then built the active miRNA-miRNA synergistic network (MMSN) integrating miRNA-miRNA synergistic pairs, which identified 16 miRNA-miRNA closed communities. Further, topology assessment, community overlapping and functional studies revealed hsa-miR-873-5p as an important pluripotent miRNA which might be hindering hESCs differentiation into Fibs by targeting regulators of epithelial to mesenchymal transition (EMT). On the other hand, synergism among hsa-miR-98-5p, hsa-let-7i-5p, hsa-let-7g-5p, hsa-miR-30a-3p and hsa-miR-29b-2-5p is predicted to be highly essential for promoting differentiation of hESCs in to Fibs. This study deepens our understanding of miRNA synergism and its regulatory impacts on properties of stem cells.
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Synergistic effects of miRNAs have been shown to be important for biological processes such as neurogenesis and human embryonic stem cell pluripotency and differentiation.
“Synergistic effects of miRNAs have been shown to be important for biological processes, such as neurogenesis (104) and human embryonic stem cell pluripotency and differentiation (105).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [105]
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Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation
O'Brien, J., Hayder, H., Zayed, Y., & Peng, C. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00402 · Cited by 5,287 · see citing works
- Authors
- Sahu, M., & Mallick, B.
- Affiliations
- National Institute of Technology Rourkela (IN)
- Corresponding author
- Mallick, Bibekanand
- ORCID
- Mallick, Bibekanand
- Venue
- International Journal of Biological Macromolecules
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 113
- Pages
- 1279-1286
- ISSN
- 0141-8130 (ISSN-L)
- OpenAlex
- W2793316263
- Cited by
- 16
- References
- 65
- Citations by year
- 2026: 1 · 2024: 3 · 2022: 4 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 2
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Biological Macromolecules (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Council of Scientific and Industrial Research (37(1586)/13/EMR-II)
- Department of Science and Technology (SR/FT/LS-77/2012)
- Department of Biotechnology (BT/PR6772/GBD/27/468/2012)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- microRNA, human embryonic stem cells, fibroblasts, pluripotency, stem cell differentiation, epithelial-mesenchymal transition, miRNA target prediction, miRNA regulatory network
- MeSH terms
- Human Embryonic Stem Cells, Cell Differentiation, Fibroblasts, Humans, Computational Biology, MicroRNAs, Gene Regulatory Networks
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