title: Global knockdown of microRNAs affects the expression of growth factors and cytokines in human adipose-derived mesenchymal stem cells.
abstract: Cell therapies utilizing mesenchymal stem cells (MSCs) have a great potential in many research and clinical settings. The mechanisms underlying the therapeutic effects of MSCs have been studied previously and the paracrine effects elicited by their production of various growth factors and cytokines were recognized as being crucial. However, the molecular controls that govern these paracrine effects remain poorly understood. To elucidate the molecular regulators of this process, we performed a global knockdown of microRNAs (miRNAs) in human adipose-derived mesenchymal stem cells (hADSCs) by inhibiting DGCR8, a key protein in miRNA biogenesis. Global disruption of miRNA biogenesis in hADSCs caused dramatic changes in the expression of subsets of growth factors and cytokines. By performing an extensive bioinformatic analysis, we were able to associate numerous putative miRNAs with these genes. Taken together, our results strongly suggest that miRNAs are essential for the production of growth factors and cytokines in hADSCs.
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center; Department of Medicine, University of Ulsan College of Medicine, Seoul 138-736, Korea.
authors.forename: Seul-Ki
authors.initials: SK
authors.lastname: Park
authors.affiliation: Institute for Innovative Cancer Research; Department of Internal Medicine, University of Ulsan College of Medicine, Seoul 138-736, Korea.
authors.forename: Jung Shin
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Institute for Innovative Cancer Research; Department of Internal Medicine; Department of Radiation Oncology; Center for Development and Commercialization of Anti-Cancer Therapeutics, University of Ulsan College of Medicine, Seoul 138-736, Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Choi
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.
authors.forename: Dalsan
authors.initials: D
authors.lastname: You
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.
authors.forename: Choung-Soo
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center; Department of Medicine, University of Ulsan College of Medicine, Seoul 138-736, Korea.
authors.forename: Nayoung
authors.initials: N
authors.lastname: Suh
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; C474043:DGCR8 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins