title: miR-196a regulates proliferation and osteogenic differentiation in mesenchymal stem cells derived from human adipose tissue.
abstract: The elucidation of the molecular mechanisms that govern the differentiation and proliferation of human adipose tissue-derived mesenchymal stem cells (hASCs) could improve hASC-based cell therapy. In this study, we examined the roles of microRNA (miRNA)-196a on hASC proliferation and osteogenic differentiation. Lentiviral overexpression of miR-196a decreased hASC proliferation and enhanced osteogenic differentiation, without affecting adipogenic differentiation. Overexpression of miR-196a decreased the protein and mRNA levels of HOXC8, a predicted target of miR-196a. HOXC8 expression was decreased during osteogenic differentiation of hASCs, and this decrease in HOXC8 expression was concomitant with an increase in the level of miR-196a. In contrast, inhibition of miR-196a with 2'-O-methyl-antisense RNA increased the protein levels of HOXC8 in treated hASCs and was accompanied by increased proliferation and decreased osteogenic differentiation. The activity of a luciferase construct containing the miR-196a target site from the HOXC8 3'UTR was lower in LV-miR196a-infected hASCs than in LV-miLacZ-infected cells. RNA interference-mediated downregulation of HOXC8 in hASCs increased their proliferation and decreased their differentiation into osteogenic cells, without affecting their adipogenic differentiation. Our data indicate that miR-196a plays a role in hASC osteogenic differentiation and proliferation, which may be mediated through its predicted target, HOXC8. This study provides us with a better knowledge of the molecular mechanisms that govern hASC differentiation and proliferation.
authors.affiliation: Department of Physiology, School of Medicine, Pusan National University, Pusan, Korea.
authors.forename: Yeon Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Sang Woo
authors.initials: SW
authors.lastname: Bae
authors.forename: Sung Sook
authors.initials: SS
authors.lastname: Yu
authors.forename: Yong Chan
authors.initials: YC
authors.lastname: Bae
authors.forename: Jin Sup
authors.initials: JS
authors.lastname: Jung
mesh_terms: D020413:3' Untranslated Regions / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010012:Osteogenesis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C489815:HOXC8 protein, human; D018398:Homeodomain Proteins; D035683:MicroRNAs; D012333:RNA, Messenger